Dimethylglycine

@article{pmid12560353,

title = {Determination of choline, betaine, and dimethylglycine in plasma by a high-throughput method based on normal-phase chromatography-tandem mass spectrometry},

author = {Pål I Holm and Per Magne Ueland and Gry Kvalheim and Ernst A Lien},

doi = {10.1373/49.2.286},

issn = {0009-9147},

year  = {2003},

date = {2003-02-01},

journal = {Clin Chem},

volume = {49},

number = {2},

pages = {286--294},

abstract = {BACKGROUND: The quaternary ammonium compounds, choline and betaine, and dimethylglycine (DMG) reside along a metabolic pathway linked to the synthesis of neurotransmitters and membrane phospholipids and to homocysteine remethylation and, therefore, folate status. Lack of a convenient, high-throughput method for the determination of these compounds has prevented population-based studies of their possible associations with lifestyle, nutrition, and chronic diseases.nnMETHODS: Serum or plasma samples were deproteinized by mixing with three volumes of acetonitrile that contained d(9)-choline and d(9)-betaine as internal standards. We used a normal-phase silica column for the separation of choline (retention time, 2.8 min), betaine (1.3 min), DMG (1.15 min), and internal standards, which were detected as positive ions by tandem mass spectroscopy in the multiple-reaction monitoring mode, using the molecular transitions m/z 104-->60 (choline), m/z 113-->69 (d(9)-choline), m/z 118-->59 (betaine), m/z 127-->68 (d(9)-betaine), and m/z 104-->58 (DMG).nnRESULTS: For all three metabolites, the assay was linear in the range 0.4-400 micromol/L, and the lower limit of the detection (signal-to-noise ratio = 5) was < or =0.3 micromol/L. The within- and between-day imprecision (CVs) was 2.1-7.2% and 3.5-8.8%, respectively. The analytical recovery was 87-105%. The fasting plasma concentrations (median, 25th-75th percentiles) were 8.0 (7.0-9.3) micromol/L for choline, 31.7 (27.0-41.1) micromol/L for betaine, and 1.66 (1.30-2.02) micromol/L for DMG in 60 healthy blood donors. In individuals who had eaten a light breakfast, plasma concentrations of all three metabolites were significantly (25-30%) higher than in fasting individuals.nnCONCLUSION: This is the first method for the combined measurement of choline, betaine, and DMG in human plasma or serum. The assay is characterized by simple sample preparation, no derivatization, high throughput, imprecision (CV) <10%, detection limits below the values seen in volunteers, and the high specificity provided by tandem mass spectroscopy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12540409,

title = {Plasma total cysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine Study},

author = {Lina El-Khairy and Stein E Vollset and Helga Refsum and Per M Ueland},

doi = {10.1093/ajcn/77.2.467},

issn = {0002-9165},

year  = {2003},

date = {2003-02-01},

journal = {Am J Clin Nutr},

volume = {77},

number = {2},

pages = {467--472},

abstract = {BACKGROUND: Total homocysteine (tHcy) is associated with pregnancy complications and adverse pregnancy outcomes. The associations of plasma total cysteine (tCys) with such outcomes have not been investigated in large populations.nnOBJECTIVE: We investigated the association between plasma tCys and pregnancy complications, congenital malformations, and other adverse pregnancy outcomes.nnDESIGN: The plasma tCys concentrations of 5883 women aged 40-42 y that were measured in 1992-1993 during a cardiovascular health screening were compared with the outcomes and complications of 14492 pregnancies in the same women that were registered in the Medical Birth Registry of Norway from 1967 to 1996.nnRESULTS: After adjustment for parity, mother's age, tHcy, total cholesterol, body mass index, smoking, and coffee drinking, high plasma tCys concentrations (above the 95th percentile) were associated with significantly higher risks of preeclampsia [n = 342; odds ratio (OR): 1.6; 95% CI: 1.1, 2.4; P = 0.03], premature delivery (n = 774; OR: 1.8; 95% CI: 1.3, 2.5; P = 0.001), and very low birth weight (n = 175; OR: 2.0; 95% CI: 1.1, 3.9; P = 0.03) than were lower plasma tCys concentrations. tCys was not associated with the risk of placental abruption. High tCys concentrations showed a weak association with congenital malformations and stillbirths with birth weight <1500 g. The associations were independent of the tHcy concentrations.nnCONCLUSION: High tCys concentrations were associated with risks of preeclampsia, premature delivery, and low birth weight.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12499324,

title = {Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: the European Concerted Action Project},

author = {Raymond Meleady and Per M Ueland and Henk Blom and Alexander S Whitehead and Helga Refsum and Leslie E Daly and Stein Emil Vollset and Cait Donohue and Belinda Giesendorf and Ian M Graham and Arve Ulvik and Ying Zhang and Anne-Lise Bjorke Monsen and },

doi = {10.1093/ajcn/77.1.63},

issn = {0002-9165},

year  = {2003},

date = {2003-01-01},

journal = {Am J Clin Nutr},

volume = {77},

number = {1},

pages = {63--70},

abstract = {BACKGROUND: Homozygotes for the thermolabile mutation (TT genotype) of the methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) enzyme have elevated plasma concentrations of the cardiovascular disease risk factor homocysteine, particularly if folate depleted.nnOBJECTIVE: We examined the relations between thermolabile MTHFR, plasma homocysteine, plasma folate, and vascular disease risk.nnDESIGN: This was a case-control comparison in 711 vascular disease cases and 747 controls from 9 European countries.nnRESULTS: The TT genotype was associated with higher homocysteine and lower plasma folate than the CC and CT genotypes in both cases and controls and a nonsignificant increase in vascular disease risk (1.26; 95% CI: 0.88, 1.81; P = 0.20). The frequency of the TT genotype in cases was not significantly different from that in controls (12.8% compared with 10.8%). After adjustment for traditional risk factors, the TT genotype was associated with an odds ratio of 1.48 (1.0, 2.20) for risk of vascular disease. This risk was attenuated after further adjustment for homocysteine. In subgroups with homocysteine concentrations >or= 9 micro mol/L, risk tended to be higher in CC than in TT subjects. However, CC subjects were characterized by a higher prevalence of the conventional risk factors associated with both elevated plasma homocysteine and serum creatinine. After adjustment, the risk of vascular disease associated with each genotype was not significantly different.nnCONCLUSIONS: There was a strong graded association between homocysteine and vascular risk in all genotypes. MTHFR genotype is a key determinant of plasma total homocysteine concentrations. The initially nonsignificant risk estimate associated with the TT genotype was strengthened after adjustment for conventional cardiovascular disease risk factors but was attenuated after adjustment for plasma folate and total homocysteine. The modest risk increase conferred by the TT genotype is mediated mainly by increased total homocysteine and low plasma folate concentrations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14599158,

title = {Routine determination of serum methylmalonic acid and plasma total homocysteine in Norway},

author = {J Schneede and P M Ueland and S I Kjaerstad},

doi = {10.1080/00365510310002059},

issn = {0036-5513},

year  = {2003},

date = {2003-01-01},

journal = {Scand J Clin Lab Invest},

volume = {63},

number = {5},

pages = {355--367},

abstract = {OBJECTIVE: To study the total number of combined analyses of methylmalonic acid (MMA) and total plasma homocysteine (tHcy) carried out during February 1998 at the Central Laboratory of Haukeland University Hospital.nnMETHODS: Laboratory data and requester comments of 2917 subjects in whom MMA was requested during February 1998, were retrieved from the laboratory information system (LIS). In 2520 cases, the results from the combined analyses of MMA and tHcy were available. Requester comments were registered in the LIS in 1084 cases. Results from additional laboratory analyses were accessible in about 10%, of cases.nnRESULTS: General practitioners requested MMA and tHcy on three main indications, i.e. low cobalamin, "control" and neurological symptoms. Metabolites were requested in twice as many women than men. Furthermore, MMA was requested in younger age groups of women compared with men. Plasma tHcy and MMA showed positive correlations with age and serum creatinine, and tHcy was generally 1-2 micromol/L higher in men than in premenopausal women. In cobalamin- (serum cobalamin > 300 pmol/L) and/or folate- (serum folate > 10 nmol/L) replete subjects, the average difference in MMA or tHcy according to the highest and lowest creatinine quartiles was 0.08 and 5-6 micromol/L, respectively. Different combinations of MMA and tHcy were evaluated by using a 5 x 5 matrix of predefined concentration intervals. Based on this matrix, cobalamin and folate deficiency could be excluded or the likely diagnoses proposed in 76% of cases. Cobalamin deficiency or folate deficiency was likely in about 7% and 12% of the subjects investigated, respectively.nnCONCLUSIONS: A combined analysis of MMA and tHcy provides complementary diagnostic information. When interpreting MMA and tHcy values, age, gender and renal function in particular must be taken into account. Typical combinations of MMA and tHcy concentration intervals could be proposed, which could either exclude deficiency or indicate likely diagnoses and/or influence of confounders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12507967,

title = {Predictors of change in plasma total cysteine: longitudinal findings from the Hordaland homocysteine study},

author = {Lina El-Khairy and Stein E Vollset and Helga Refsum and Per M Ueland},

doi = {10.1373/49.1.113},

issn = {0009-9147},

year  = {2003},

date = {2003-01-01},

journal = {Clin Chem},

volume = {49},

number = {1},

pages = {113--120},

abstract = {BACKGROUND: Total cysteine (tCys) in plasma has recently been linked to cardiovascular risk and is also associated with cardiovascular risk factors, including body mass index (BMI) and cholesterol. Changes and predictors of change in tCys concentrations over a mean follow-up time of 6.0 (5.2-7.2) years were assessed in this study.nnMETHODS: Baseline data from the Hordaland Homocysteine Study recorded in 1992-1993 included tCys, total homocysteine (tHcy), and various lifestyle and cardiovascular risk factors. In 1998-1999, the same measurements were repeated in 3,732 individuals born in 1950-1951 and 3,339 individuals born in 1925-1927. Most of the statistical analyses were done separately in the four age and sex groups.nnRESULTS: The overall mean values of tCys were higher at follow-up [mean (SD), 296 (41) micro mol/L] than at baseline [278 (36.5) micro mol/L]; P <0.0001. The mean percentage of increase in tCys in the different age and sex groups ranged from 4.9% to 8.5%. There was a significant correlation between the tCys values measured on the two occasions (Spearman correlation coefficient, 0.55-0.59 in the different age and sex groups; P <0.0001). The change in tCys correlated with changes in BMI, cholesterol, and diastolic blood pressure in the younger age group, whereas only changes in BMI predicted changes in tCys in the older age group.nnCONCLUSIONS: tCys increased in the 6 years between the two measurements. Factors related to the baseline tCys values, including BMI and the change in BMI, predicted the tCys changes over time.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12507972,

title = {Plasma vitamin B6 vitamers before and after oral vitamin B6 treatment: a randomized placebo-controlled study},

author = {Mustafa Vakur Bor and Helga Refsum and Marianne R Bisp and Øyvind Bleie and Jorn Schneede and Jan Erik Nordrehaug and Per Magne Ueland and Ottar Kjell Nygard and Ebba Nexø},

doi = {10.1373/49.1.155},

issn = {0009-9147},

year  = {2003},

date = {2003-01-01},

journal = {Clin Chem},

volume = {49},

number = {1},

pages = {155--161},

abstract = {BACKGROUND: Vitamin B(6) has attracted renewed interest because of its role in homocysteine metabolism and its possible relation to cardiovascular risk. We examined the plasma B(6) vitamers, pyridoxal 5'-phosphate (PLP), pyridoxal (PL), pyridoxine (PN), and 4-pyridoxic acid (4-PA) before and after vitamin B(6) supplementation.nnMETHODS: Patients (n = 90; age range, 38-80 years) undergoing coronary angiography (part of the homocysteine-lowering Western Norway B-Vitamin Intervention Trial) were allocated to the following daily oral treatment groups: (A), vitamin B(12) (0.4 mg), folic acid (0.8 mg), and vitamin B(6) (40 mg); (B), vitamin B(12) and folic acid; (C), vitamin B(6); or (D), placebo. EDTA blood was obtained before treatment and 3, 14, 28, and 84 days thereafter.nnRESULTS: Before treatment, PLP (range, 5-111 nmol/L) and 4-PA (6-93 nmol/L) were the predominant B(6) vitamers identified in plasma. During the 84-day study period, the intraindividual variation (CV) in patients not treated with vitamin B(6) (groups B and D) was 45% for PLP and 67% for 4-PA. Three days after the start of treatment, the increases in concentration were approximately 10-, 50-, and 100-fold for PLP, 4-PA, and PL, respectively. No significant additional increase was observed at the later time points. The PLP concentration correlated to the concentrations of 4-PA and PL before treatment, but not after treatment. The PL concentration correlated with 4-PA before and after treatment.nnCONCLUSIONS: Vitamin B(6) treatment has an immediate effect on the concentrations and the forms of B(6) vitamers present in plasma, and the changes remain the same during prolonged treatment. Our results suggest that the B(6) vitamers in plasma reflect vitamin B(6) intake.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12324494,

title = {Holo-transcobalamin is an early marker of changes in cobalamin homeostasis. A randomized placebo-controlled study},

author = {Ebba Nexo and Anne-Mette Hvas and Øyvind Bleie and Helga Refsum and Sergey N Fedosov and Stein Emil Vollset and Jorn Schneede and Jan Erik Nordrehaug and Per Magne Ueland and Ottar Kjell Nygard},

issn = {0009-9147},

year  = {2002},

date = {2002-10-01},

journal = {Clin Chem},

volume = {48},

number = {10},

pages = {1768--1771},

abstract = {BACKGROUND: We examined the effect of oral vitamin B(12) treatment on fluctuations in plasma total cobalamin and its binding proteins transcobalamin (TC) and haptocorrin (HC).nnMETHODS: Patients (n = 88; age range, 38-80 years) undergoing coronary angiography (part of the homocysteine-lowering Western Norway B-Vitamin Intervention Trial) were allocated to daily oral treatment with (a) vitamin B(12) (0.4 mg), folic acid (0.8 mg), and vitamin B(6) (40 mg); (b) vitamin B(12) and folic acid; (c) vitamin B(6); or (d) placebo. EDTA blood was obtained before treatment and 3, 14, 28, and 84 days thereafter.nnRESULTS: The intraindividual variation for patients not treated with B(12) was approximately 10% for plasma total cobalamin, total TC, apo-TC, and apo-HC, and <20% for holo-TC and TC saturation. In B(12)-treated patients, the maximum change in concentrations was observed already after 3 days for total TC (-16%), holo-TC (+54%), and TC saturation (+82%). At this time holo-HC (+20%) and plasma total cobalamin (+28%) showed an initial burst, but had increased further at 84 days. All changes were highly significant compared with the control group (P <0.0001).nnCONCLUSIONS: Oral vitamin B(12) treatment produces maximal effects on total TC, holo-TC, and TC saturation within 3 days, whereas maximal increases in holo-HC and plasma total cobalamin occur later. The results support the view that holo-TC is an early marker of changes in cobalamin homeostasis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12194936,

title = {Riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in human plasma and erythrocytes at baseline and after low-dose riboflavin supplementation},

author = {Steinar Hustad and Michelle C McKinley and Helene McNulty and Jørn Schneede and J J Strain and John M Scott and Per Magne Ueland},

issn = {0009-9147},

year  = {2002},

date = {2002-09-01},

journal = {Clin Chem},

volume = {48},

number = {9},

pages = {1571--1577},

abstract = {BACKGROUND: Vitamin B(2) exists in blood as riboflavin and its cofactors, flavin mononucleotide (FMN) and FAD. The erythrocyte glutathione reductase activation coefficient (EGRAC) has traditionally been used to assess vitamin B(2) status in humans. We investigated the relationships of EGRAC and plasma and erythrocyte concentrations of riboflavin, FMN, and FAD in elderly volunteers and their responses to riboflavin administration.nnMETHODS: EGRAC and plasma and erythrocyte concentrations of riboflavin, FMN, and FAD were determined in 124 healthy individuals with a mean age of 69 years. The same measurements were made in a subgroup of 46 individuals with EGRAC > or =1.20 who participated in a randomized double-blind 12-week intervention study and received riboflavin (1.6 mg/day; n = 23) or placebo (n = 23).nnRESULTS: Median plasma concentrations were 10.5 nmol/L for riboflavin, 6.6 nmol/L for FMN, and 74 nmol/L for FAD. In erythrocytes, there were only trace amounts of riboflavin, whereas median FMN and FAD concentrations were 44 and 469 nmol/L, respectively. Erythrocyte FMN and FAD correlated with each other and with EGRAC and plasma riboflavin (P <0.05). All variables except plasma FAD responded significantly to riboflavin supplementation compared with placebo (P < or =0.04). The strongest increases were for riboflavin in plasma (83%) and for FMN in erythrocytes (87%).nnCONCLUSIONS: Concentrations of all B(2) vitamers except plasma FAD are potential indicators of vitamin B(2) status, and plasma riboflavin and erythrocyte FMN may be useful for the assessment of vitamin B(2) status in population studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12119198,

title = {Homocysteine levels in men and women of different ethnic and cultural background living in England},

author = {Francesco P Cappuccio and Rachel Bell and Ivan J Perry and Julie Gilg and Per M Ueland and Helga Refsum and Giuseppe A Sagnella and Steve Jeffery and Derek G Cook},

doi = {10.1016/s0021-9150(02)00024-2},

issn = {0021-9150},

year  = {2002},

date = {2002-09-01},

journal = {Atherosclerosis},

volume = {164},

number = {1},

pages = {95--102},

abstract = {This population-based cross-sectional study in South London looks at the total homocysteine (tHcy) levels in groups of different ethnic background and the possible role of environmental factors and the 677C-->T genetic polymorphism of the methylenetetrahydrofolate reductase (MTHFR). Fasting plasma tHcy was measured in 1392 men and women, age 40-59 years; 475 were white, 465 of African origin (of whom 180 were West Africans and 280 Caribbeans) and 452 South Asian (of whom 222 were Hindus and 167 Muslims). The homozygous MTHFR TT variant had observed frequencies of 0.10 in whites, 0.01 in people of African origin and 0.02 in South Asians (P<0.001). tHcy levels were 16% (95% CI 8-26) higher amongst TT than CC. tHcy levels were 25% (21-29) higher in men than women. Levels were significantly higher in South Asians than whites (8% [3-13]). Vegetarians had higher levels than non-vegetarians (25% [18-33]). These differences were present after adjustments for age, sex, smoking, body mass index (BMI), MTHFR 677C-->T polymorphism and socio-economic status. Compared with whites (10.0 [9.7-10.3] micromol/l), and allowing for confounders, Hindus had significantly higher levels of tHcy (12.1 [11.6-12.6] micromol/l). This difference was attenuated by the inclusion of vegetarianism in the model (11.3 [10.8-11.9] micromol/l). In contrast Muslims had similar tHcy levels to whites while both West Africans and Caribbeans had slightly lower levels, though differences were not significant. The reported higher levels of tHcy in South Asians are due to high levels amongst Hindus only. They are in part accounted for by their vegetarianism. These differences in tHcy are large enough to be important contributors to the risk of vascular disease and may be preventable by simple targeted population strategies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12076236,

title = {Plasma total homocysteine and hospitalizations for cardiovascular disease: the Hordaland Homocysteine Study},

author = {Eha Nurk and Grethe S Tell and Stein Emil Vollset and Ottar Nygård and Helga Refsum and Per M Ueland},

doi = {10.1001/archinte.162.12.1374},

issn = {0003-9926},

year  = {2002},

date = {2002-06-01},

journal = {Arch Intern Med},

volume = {162},

number = {12},

pages = {1374--1381},

abstract = {BACKGROUND: Elevated total plasma homocysteine (tHcy) level is a risk factor for occlusive disease in the coronary, cerebral, and peripheral vessels and is related to several lifestyle factors associated with cardiovascular disease (CVD).nnOBJECTIVE: To examine the association of a single tHcy measurement on subsequent hospitalizations due to CVD.nnMETHODS: A population-based prospective cohort study was conducted from April 1, 1992, to May 31, 1998 (mean follow-up, 5.3 years) in western Norway. The study included 17 361 individuals aged 40 to 42 or 65 to 67 years at baseline. Main outcome measure was CVD as the main hospital discharge diagnosis or coronary revascularization procedures (denoted "CVD hospitalizations") during follow-up (n = 1275).nnRESULTS: At baseline, participants with preexisting CVD had higher mean tHcy values than individuals without CVD. Risk of CVD hospitalizations increased significantly with increasing baseline tHcy only in the oldest age group. Here, multiple risk factor-adjusted hospitalization rate ratios in 5 tHcy categories (<9, 9-11.9, 12-14.9, 15-19.9, and >or=20 micromol/L [to convert tHcy to milligrams per liter, divide by 7.397]) were as follows: 1 (reference level), 1.00, 1.34, 1.67, and 1.94, respectively (P for trend <.001). The relation between tHcy level and CVD hospitalizations was significantly stronger among individuals with preexisting CVD than those without (hospitalization rate ratio per 5-micromol/L tHcy increment, 1.29 vs 1.10; P for interaction,.02).nnCONCLUSIONS: Plasma tHcy level is a strong predictor of CVD hospitalizations only in elderly individuals, and especially among those with preexisting CVD. Our findings are compatible with the theory that tHcy interacts with conventional CVD risk factors to provoke the acute event of CVD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid17903848,

title = {Effects of vitamin therapy on plasma total homocysteine, endothelial injury markers, and fibrinolysis in stroke patients},

author = {Richard F Macko and Steven J Kittner and Frederick M Ivey and Anne Epstein and Mary J Sparks and J Richard Hebel and Constance C Johnson and Robert J Wityk and Per M Ueland and Helga Refsum},

doi = {10.1053/jscd.2002.123968},

issn = {1532-8511},

year  = {2002},

date = {2002-01-01},

journal = {J Stroke Cerebrovasc Dis},

volume = {11},

number = {1},

pages = {1--8},

abstract = {Hyperhomocystinemia linked to B-vitamin deficiency is prevalent and associated with increased risk for stroke. While in vitro studies suggest homocysteine directly injures vascular endothelial thrombomodulin (TM), inhibits vonWillebrand factor (vWF) synthesis, and blocks tissue plasminogen activator (t-PA) receptor binding, these mechanisms and their reversibility by vitamin therapy are not established in humans. We investigated the effects of high-dose B-vitamin therapy on endogenous fibrinolysis and endothelial injury markers by randomizing 50 nonvitamin users with prior ischemic stroke to 3 months of treatment with multivitamins either containing folate (5 mg), B6 (100 mg), and B12 (1 mg), or lacking these components. Fasting before noon and post-methionine load plasma total homocysteine (tHcy), t-PA antigen levels, t-PA and plasminogen activator inhibitor (PAI) activities, total vWF antigen, and TM levels were measured before and after vitamin therapy. The primary analysis between treatment groups across time revealed no significant changes (P > .1) for any hematologic variables. However, within-groups analysis showed reductions of 23% in plasma TM (P < .005) and 27% in fasting tHcy levels (P < .0001) and a paradoxical 30% rise in vWF antigen levels (P < .05) after high-dose B-vitamin, treatment with no changes in controls. Pooled data revealed a significant and reproducible 20% to 28% decline in plasma t-PA activity after methionine load (n = 49, P < .02). Our findings demonstrate methionine load lowers plasma t-PA activity by a plasminogen activator inhibitor (PAI-1) independent mechanism that is not attenuated by 3 months of high-dose B-vitamin treatment. While not improving endogenous fibrinolysis profiles, these results provide initial evidence that B-vitamin treatment may selectively alter markers of vascular endothelial injury after stroke.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid11795809,

title = {Uracil in human DNA from subjects with normal and impaired folate status as determined by high-performance liquid chromatography-tandem mass spectrometry},

author = {Jicun Ren and Arve Ulvik and Helga Refsum and Per Magne Ueland},

doi = {10.1021/ac010556k},

issn = {0003-2700},

year  = {2002},

date = {2002-01-01},

journal = {Anal Chem},

volume = {74},

number = {1},

pages = {295--299},

abstract = {A sensitive and selective method for determination of the uracil content in human DNA was first developed on the basis of high-performance liquid chromatography-tandem mass spectrometry. Uracil was excised from DNA using uracil DNA glycosylase. The released uracil was derivatized with 4-bromomethyl-7-methoxycoumarin, thereby forming bis-N,N'-(4-methylene-7-methoxycoumaryl)-uracil (uracil-MMC). 15N2-Uracil was used as an internal standard. The analytes were separated on an Adsorbsphere XL ODS column. A SCIEX API III tandem mass spectrometer equipped with a turbo ion-spray interface was used as the detector. Multiple reaction monitoring using the parent --> product ion combinations of m/z 489 --> 232 and 491 --> 233 were used to detect uracil-MMC and the internal standard, respectively. The detection limit for this assay is <1.0 x 10(-10) mol/L uracil, and the linearity is from 1.0 x 10(-10) to 2.5 x 10(-6) mol/L. The method was used for determination of uracil in human DNA. Our data show that the uracil levels in human DNA isolated from peripheral white blood cells did not differ between subjects with folate deficiency and subjects with normal red cell folate levels.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid11673381,

title = {Single nucleotide polymorphism (SNP) genotyping in unprocessed whole blood and serum by real-time PCR: application to SNPs affecting homocysteine and folate metabolism},

author = {A Ulvik and P M Ueland},

issn = {0009-9147},

year  = {2001},

date = {2001-11-01},

journal = {Clin Chem},

volume = {47},

number = {11},

pages = {2050--2053},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid11737234,

title = {Total homocysteine is making its way into pediatric laboratory diagnostics},

author = {P M Ueland and A L Bjørke Monsen},

doi = {10.1046/j.1365-2362.2001.00918.x},

issn = {0014-2972},

year  = {2001},

date = {2001-11-01},

journal = {Eur J Clin Invest},

volume = {31},

number = {11},

pages = {928--930},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid11533328,

title = {Determinants of cobalamin status in newborns},

author = {A L Bjørke Monsen and P M Ueland and S E Vollset and A B Guttormsen and T Markestad and E Solheim and H Refsum},

doi = {10.1542/peds.108.3.624},

issn = {1098-4275},

year  = {2001},

date = {2001-09-01},

journal = {Pediatrics},

volume = {108},

number = {3},

pages = {624--630},

abstract = {OBJECTIVE: Cobalamin deficiency accompanied by bone marrow dysfunction and impaired central nervous system development has been reported in infants who were born to mothers with low cobalamin intake. We investigated the relation between cobalamin status in newborns and in their healthy mothers who consumed an omnivorous diet.nnMETHODS: Serum cobalamin and the functional markers plasma methylmalonic acid (MMA) and total homocysteine (tHcy) were determined in 173 newborns and their mothers. Forty-five children and mothers were reinvestigated after 6 weeks.nnRESULTS: At birth, median (interquartile range) serum cobalamin levels were 245 (175-323) pmol/L in the mothers and 314 (238-468) pmol/L in the newborns. In the neonates, serum cobalamin, but not folate, was inversely associated with MMA and tHcy. Among maternal factors, low serum cobalamin was the strongest predictor of impaired cobalamin function (defined as low cobalamin, high tHcy, or high MMA levels) in the newborns. After 6 weeks, the maternal cobalamin levels had increased (to 421 [271-502] pmol/L), whereas the newborn levels had declined (to 230 [158-287] pmol/L). In the same interval, the infants had a marked increase in plasma MMA (from 0.29 [0.24-0.38] to 0.81 [0.37-1.68] micromol/L). At 6 weeks, parity was a strong predictor of cobalamin status in the infant.nnCONCLUSION: The cobalamin status in the neonatal period is strongly associated with maternal cobalamin status and parity. A reduction in serum cobalamin and an increase in metabolite levels are consistent with impaired cobalamin function in a significant portion of the infants who were born to healthy, nonvegetarian mothers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid11514424,

title = {Plasma total homocysteine in hyper- and hypothyroid patients before and during 12 months of treatment},

author = {B G Nedrebø and O Nygård and P M Ueland and E A Lien},

issn = {0009-9147},

year  = {2001},

date = {2001-09-01},

journal = {Clin Chem},

volume = {47},

number = {9},

pages = {1738--1741},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid11470726,

title = {Hyperhomocysteinemia and elevated methylmalonic acid indicate a high prevalence of cobalamin deficiency in Asian Indians},

author = {H Refsum and C S Yajnik and M Gadkari and J Schneede and S E Vollset and L Orning and A B Guttormsen and A Joglekar and M G Sayyad and A Ulvik and P M Ueland},

doi = {10.1093/ajcn/74.2.233},

issn = {0002-9165},

year  = {2001},

date = {2001-08-01},

journal = {Am J Clin Nutr},

volume = {74},

number = {2},

pages = {233--241},

abstract = {BACKGROUND: In India, most people adhere to a vegetarian diet, which may lead to cobalamin deficiency.nnOBJECTIVE: The objective was to examine indicators of cobalamin status in Asian Indians.nnDESIGN: The study population included 204 men and women aged 27-55 y from Pune, Maharashtra, India, categorized into 4 groups: patients with cardiovascular disease (CVD) and diabetes, patients with CVD but no diabetes, patients with diabetes but no CVD, and healthy subjects. Data on medical history, lifestyle, and diet were obtained by interviews and questionnaires. Blood samples were collected for measurement of serum or plasma total cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), and total homocysteine (tHcy) and hemetologic indexes.nnRESULTS: MMA, tHcy, total cobalamin, and holoTC did not differ significantly among the 4 groups; therefore, the data were pooled. Total cobalamin showed a strong inverse correlation with tHcy (r = -0.59) and MMA (r = -0.54). Forty-seven percent of the subjects had cobalamin deficiency (total cobalamin <150 pmol/L), 73% had low holoTC (<35 pmol/L), 77% had hyperhomocysteinemia (tHcy >15 micromol/L), and 73% had elevated serum MMA (>0.26 micromol/L). These indicators of impaired cobalamin status were observed in both vegetarians and nonvegetarians. Folate deficiency was rare and only 2.5% of the subjects were homozygous for the MTHFR 677C-->T polymorphism.nnCONCLUSIONS: About 75% of the subjects had metabolic signs of cobalamin deficiency, which was only partly explained by the vegetarian diet. If impaired cobalamin status is confirmed in other parts of India, it may have important health implications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid11451728,

title = {Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocysteine Study},

author = {S E Vollset and H Refsum and A Tverdal and O Nygård and J E Nordrehaug and G S Tell and P M Ueland},

doi = {10.1093/ajcn/74.1.130},

issn = {0002-9165},

year  = {2001},

date = {2001-07-01},

journal = {Am J Clin Nutr},

volume = {74},

number = {1},

pages = {130--136},

abstract = {BACKGROUND: Few population-based studies have assessed relations between plasma or serum total homocysteine (tHcy) and all-cause mortality.nnOBJECTIVE: Our goal was to study associations between plasma tHcy and all-cause, cardiovascular, and noncardiovascular mortality.nnDESIGN: This was a prospective cohort study of 2127 men and 2639 women aged 65-67 y in 1992-1993 when they were recruited as part of a population-based national cardiovascular screening program carried out in Hordaland County, Norway.nnRESULTS: During a median of 4.1 y of follow-up, 162 men and 97 women died. A strong relation was found between plasma tHcy and all-cause mortality. The association was highly significant for noncardiovascular and for cardiovascular causes of death. In a comparison of individuals having tHcy concentrations of 9.0-11.9, 12.0-14.9, 15.0-19.9, or > or = 20 micromol/L with individuals having a tHcy concentration < 9 micromol/L, adjusted mortality ratios were 1.4, 1.9, 2.3, and 3.6 (P for trend = 0.0002) for noncardiovascular and 1.3, 2.1, 2.6, and 3.5 (P for trend = 0.0002) for cardiovascular causes of death. A tHcy increment of 5 micromol/L was associated with a 49% (95% CI: 28%, 72%) increase in all-cause mortality, a 50% (95% CI: 21%, 85%) increase in cardiovascular mortality (121 deaths), a 26% (95% CI: -2%, 63%) increase in cancer mortality (103 deaths), and a 104% (95% CI: 44%, 289%) increase in noncancer, noncardiovascular mortality (33 deaths).nnCONCLUSION: Plasma tHcy is a strong predictor of both cardiovascular and noncardiovascular mortality in a general population of 65-72-y-olds. These results should encourage studies of tHcy in a wider perspective than one confined to cardiovascular disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid11424140,

title = {Smoking, folate and methylenetetrahydrofolate reductase status as interactive determinants of adenomatous and hyperplastic polyps of colorectum},

author = {A Ulvik and E T Evensen and E A Lien and G Hoff and S E Vollset and B M Majak and P M Ueland},

doi = {10.1002/ajmg.1370},

issn = {0148-7299},

year  = {2001},

date = {2001-07-01},

journal = {Am J Med Genet},

volume = {101},

number = {3},

pages = {246--254},

abstract = {Most studies demonstrate increased risk of colorectal cancer (CRC) and adenomas in folate-deficient subjects or that high folate intake may afford some protection. Smoking increases such risk in some but not all studies. We investigated whether smoking, folate status and methylenetetrahydrofolate reductase (MTHFR) genotype predict the risk of adenomatous and hyperplastic polyps of colorectum. By colonoscopy, the type, number, size and extent of dysplasia of colorectal polyps were assessed in 443 subjects aged 63-72 years. We also determined RBC folate and the C667T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Smoking, folate status and the C677T MTHFR polymorphism were strong, interactive determinants of high-risk adenomas (HRAs, defined as adenomas > or =10 mm in diameter, adenomas with villous components or with severe dysplasia). The risk was particularly high in smokers with low folate and the CT/TT genotype (risk category T) and in smokers with high folate and the CC genotype (risk category C). With non-smokers with low folate and the CC genotype as reference, the odds ratios (OR, 95% CI) were 8.7 (2.5-29.7) in category T and 9.9 (2.6-38.4) in category C. Notably, this risk pattern was also observed for hyperplastic polyps. In conclusion, in smokers, high folate status may confer increased or decreased risk for HRAs, depending on the MTHFR genotype. These data demonstrate the strong gene-nutrition interaction involving the C677T MTHFR polymorphism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}