Genome-wide Association Study of Vitamin B6, Vitamin B12, Folate, and Homocysteine Blood Concentrations
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PROVIDER: S-EPMC2683944 | biostudies-literature | 2009 May
REPOSITORIES: biostudies-literature
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Project description:The B vitamins are components of one-carbon metabolism (OCM) that contribute to DNA synthesis and methylation. Homocysteine, a by-product of OCM, has been associated with coronary heart disease, stroke and neurological disease. To investigate genetic factors that affect circulating vitamin B6, vitamin B12, folate and homocysteine, a genome-wide association analysis was conducted in the InCHIANTI (N = 1175), SardiNIA (N = 1115), and BLSA (N = 640) studies. The top loci were replicated in an independent sample of 687 participants in the Progetto Nutrizione study. Polymorphisms in the ALPL gene (rs4654748, p = 8.30 x 10(-18)) were associated with vitamin B6 and FUT2 (rs602662, [corrected] p = 2.83 x 10(-20)) with vitamin B12 serum levels. The association of MTHFR, a gene consistently associated with homocysteine, was confirmed in this meta-analysis. The ALPL gene likely influences the catabolism of vitamin B6 while FUT2 interferes with absorption of vitamin B12. These findings highlight mechanisms that affect vitamin B6, vitamin B12 and homocysteine serum levels.
| S-EPMC2667971 | biostudies-literature
Project description:ImportanceThe associations of B vitamin status with metabolic syndrome (MetS) incidence among the US population remain unclear.ObjectiveTo investigate intakes and serum concentrations of folate, vitamin B6, and vitamin B12 in association with MetS risk in a large US cohort.Design, setting, and participantsThis prospective study included Black and White young adults in the US who were enrolled from 1985 to 1986 and studied until 2015 to 2016. Diet was assessed using a validated diet history at examination years 0, 7, and 20. Serum concentrations of folate, vitamin B6, and vitamin B12 were assayed at examination years 0, 7, and 15 in a subset of 1430 participants. MetS was ascertained by clinic and laboratory measurements and self-reported medication use. Data were analyzed between January and July 2021.ExposuresIntakes and serum levels of folate, vitamin B6, and vitamin B12.Main outcomes and measuresMultivariable Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs for the associations of energy-adjusted B vitamin intakes or serum B vitamin levels with incident MetS.ResultsThe study included 4414 participants, with 2225 Black individuals (50.4%) and 2331 women (52.8%). The mean (SD) age at baseline was 24.9 (3.6) years. A total of 1240 incident MetS cases occurred during the 30 years (mean [SD], 22.1 [9.5] years) of follow-up. Compared with the lowest quintile of each energy-adjusted B vitamin intake, the HRs for incident MetS in the highest quintile were 0.39 (95% CI, 0.31-0.49) for folate (P for trend < .001), 0.61 (95% CI, 0.46-0.81) for vitamin B6 (P for trend = .002), and 0.74 (95% CI, 0.58-0.95) for vitamin B12 (P for trend = .008) after adjustment for potential confounders. Similarly, significant inverse associations were observed in the subset with serum data on these B vitamins (folate: HR, 0.23; 95% CI, 0.17-0.33; P for trend < .001; vitamin B6: HR, 0.48; 95% CI, 0.34-0.67; P for trend < .001; and vitamin B12: HR, 0.70; 95% CI, 0.51-0.96; P for trend = .01).Conclusions and relevanceThis prospective cohort study found that intakes and serum concentrations of folate, vitamin B6, and vitamin B12 were inversely associated with incident MetS among Black and White young adults in the US.
| S-EPMC9856626 | biostudies-literature
Project description:BackgroundDiverse conclusions have been drawn regarding the association of homocysteine (HCY) deficiency and supplements of B vitamins with fracture incidence in older adults. The aim of this meta-analysis was to investigate the association of HCY and B vitamins (folate, vitamin B12, and B6) with fracture incidence in older adults and whether supplements of B vitamins reduce the risk of fracture.MethodsThe PubMed, Embase, and Cochrane library databases were systematically searched from their inception dates to 1 July 2019 to identify relevant published articles. Meta-analysis was performed to pool hazard ratios (HRs) or risk ratios (RRs) and 95% confidence intervals (CIs) using a random effects model.ResultsA total of 28 studies fulfilled the inclusion criteria. High serum HCY was an independent risk factor for fractures in older persons (HR =1.25, 95% CI: 1.12 to 1.40), but only at the highest quartile level (>15 µmol/L) (HR =1.71, 95% CI: 1.37 to 2.12), rather than the second and third quartile. Multiple sensitivity and subgroup analyses supported the consistency and stability of this result. A severe deficiency of folate, instead of vitamin B12 and B6, was found to increase the risk of fracture in older adults (HR =1.46, 95% CI: 1.06 to 2.02; 1.24, 95% CI: 0.79 to 1.95; 1.36, 95% CI: 0.90 to 2.06, respectively). For the interventional effect, there was no significant association of combined folate and vitamin B12, combined folate, vitamin B12 and B6, or single vitamin B6 supplementation with the decrease of fracture risk.DiscussionThis meta-analysis revealed that significantly elevated serum level of HCY is positively associated with fracture incidence in older adults, yet the necessity and threshold for intervention by B vitamins require further large-scale high-quality clinical trials to validate.Prospero identifierCRD42019122586.
| S-EPMC8350623 | biostudies-literature
Project description:Background & aimsSuboptimal circulating vitamin B12, folate and homocysteine concentrations during fetal life seem to be associated with cardiometabolic health at school-age. We examined whether fetal exposure to lower circulating vitamin B12 and folate concentrations and higher circulating homocysteine concentrations is also associated with early signs of atherosclerosis at school-age.MethodsThis study among 3826 school-age children and their mothers was embedded in the Generation R Study, a population-based prospective cohort study from early pregnancy onwards. We examined the associations of early-pregnancy and cord blood serum total and active B12 and plasma folate and homocysteine concentrations with common carotid artery intima-media thickness and distensibility in the children aged ten years.ResultsAs compared to normal early-pregnancy serum total B12 concentrations (≥145 pmol/L), low serum total B12 concentrations (<145 pmol/L) were associated with higher carotid intima-media thickness in the children at school-age (difference 0.09 standard deviations score (SDS); 95% confidence interval (CI): 0.01, 0.16). As compared to normal early-pregnancy plasma folate concentrations (≥8 nmol/L), low plasma folate concentrations (<8 nmol/L) were associated with lower carotid distensibility in the children at school-age (difference -0.16 SDS; 95% CI: -0.28, -0.04). Early-pregnancy circulating total and active B12, folate and homocysteine concentrations measured continuously were not associated with carotid intima-media thickness or carotid distensibility in the children at school-age. One SDS higher plasma homocysteine concentrations measured in cord blood at birth was associated with a -0.05 SDS (95% CI: -0.09, -0.02) lower carotid distensibility at school-age. Cord blood total and active B12 and folate concentrations were not associated with carotid intima-media thickness or carotid distensibility at school-age.ConclusionsCirculating total B12, folate and homocysteine concentrations during fetal life seem to be associated with markers of subclinical atherosclerosis at school-age. Further studies need to examine the causality and mechanisms underlying these associations.
| S-EPMC7613758 | biostudies-literature
Project description:BackgroundCirculating folate, vitamin B12 and homocysteine concentrations during fetal development have been associated with health outcomes in childhood. Changes in fetal DNA methylation may be an underlying mechanism. This may be reflected in altered epigenetic aging of the fetus, as compared to chronological aging. The difference between gestational age derived in clinical practice and gestational age predicted from neonatal DNA methylation data is referred to as gestational age acceleration. Differences in circulating folate, vitamin B12 and homocysteine concentrations during fetal development may be associated with gestational age acceleration.ResultsUp to 1346 newborns participating in the Generation R Study, a population-based prospective cohort study, had both cord blood DNA methylation data available and information on plasma folate, serum total and active B12 and plasma homocysteine concentrations, measured in early pregnancy and/or in cord blood. A subgroup of 380 newborns had mothers with optimal pregnancy dating based on a regular menstrual cycle and a known date of last menstrual period. For comparison, gestational age acceleration was calculated based the method of both Bohlin and Knight. In the total study population, which was more similar to Bohlin's training population, one standard deviation score (SDS) higher maternal plasma homocysteine concentrations was nominally associated with positive gestational age acceleration [0.07 weeks, 95% confidence interval (CI) 0.02, 0.13] by Bohlin's method. In the subgroup with pregnancy dating based on last menstrual period, the method that was also used in Knight's training population, one SDS higher cord serum total and active B12 concentrations were nominally associated with negative gestational age acceleration [(- 0.16 weeks, 95% CI - 0.30, - 0.02) and (- 0.15 weeks, 95% CI - 0.29, - 0.01), respectively] by Knight's method.ConclusionsWe found some evidence to support associations of higher maternal plasma homocysteine concentrations with positive gestational age acceleration, suggesting faster epigenetic than clinical gestational aging. Cord serum vitamin B12 concentrations may be associated with negative gestational age acceleration, indicating slower epigenetic than clinical gestational aging. Future studies could examine whether altered fetal epigenetic aging underlies the associations of circulating homocysteine and vitamin B12 blood concentrations during fetal development with long-term health outcomes.
| S-EPMC8082638 | biostudies-literature
Project description:Deficiency of vitamin B6 and vitamin B12, mostly in vegetarians, is found to be associated with depression and adverse neurological function. We investigated whether vitamin B6, B12, and folate have an effect on brain structure, especially among depressed people who follow a specific diet. The study sample comprised 9426 participants from the UK Biobank cohort with a mean age of 62.4 years. A generalized linear model controlling for age, sex, body mass index, ethnicity, town send deprivation index, educational qualification, smoking, and alcohol intake was used to test the association between study groups and structural brain volumes. Depression was more prevalent, and intake of vitamin B6 and B12 was lower among vegetarians, while non-vegetarians had a lower intake of folate. Overall, no significant association was observed between vitamin B6, B12, and folate intakes and both global and subcortical brain volumes among participants with depression. However, vitamin B12 intake was positively associated with right pallidum among non-depressed participants, and a significant interaction between vitamin B12 intake and depression status on the right pallidum was observed. Also, a significant interaction between folate intake and depression status on grey matter (GM) volume and left thalamus was observed. Upon diet stratification, folate intake is associated with total brain volume and GM volume among vegetarians with depression. Furthermore, no significant associations were observed for subcortical regions. Our findings suggest that dietary intake of vitamin B6 and B12 might have an effect on brain structure. Vegetarians, particularly those who suffer from depression may benefit from supplementing their diets with vitamins B6, B12, and folate to ensure brain health. Further studies, especially with a larger sample size and longitudinal design, are needed to confirm these findings.
| S-EPMC8225207 | biostudies-literature
Project description:Homocysteine, inversely related to folate and vitamin B12, is an independent risk factor for several age-related disorders. However, little is known about the association of homocysteine and related vitamins with osteoarthritis (OA). This study aimed to elucidate the potential causal effects of homocysteine, folate, and vitamin B12 on site- and gender-specific OA by applying the two-sample Mendelian randomization (MR) approach. Genetically predicted homocysteine showed adverse effects on overall OA (95% confidence interval (CI): 1.044-1.155), knee OA (95% CI: 1.000-1.167), hip OA (95% CI: 1.057-1.297), and spine OA (95% CI: 1.017-1.216). Genetically predicted folate showed protective effects on overall OA (95% CI: 0.783-0.961) and spine OA (95% CI: 0.609-0.954). Folate (95% CI: 0.887-1.004) and vitamin B12 (95% CI: 0.886-1.009) showed a protective trend against knee OA. The patterns of associations were site and gender specific. In conclusion, homocysteine had adverse effects on OA, especially on OA at weight-bearing joints and in females. Folate and vitamin B12 had protective effects on OA. Homocysteine-lowering interventions may be a potential option in the treatment and prevention of OA.
| S-EPMC10096814 | biostudies-literature
Project description:Smoking exposure is associated with pregnancy complications, as are levels of folate, vitamin B12, and homocysteine. In nonpregnant adults, smoking exposure is associated negatively with folate and vitamin B12 levels and positively with homocysteine levels. A complete overview of the literature on this topic in pregnant women is lacking. To evaluate evidence of associations of maternal smoking exposure during pregnancy and levels of folate, homocysteine, and vitamin B12 in pregnancy and in cord blood, we searched MEDLINE, Embase, CINAHL, Cochrane, Scopus, Web of Science, and reference lists of relevant studies until August 2017. We selected studies in pregnant women describing the association of passive or active smoking and levels of folate, homocysteine, and/or vitamin B12. Data were extracted by two independent reviewers. We included 32 studies of 2,015 identified references with a total of 37,822 participants and more than 6,000 smokers. Twenty-eight studies measured folate, 14 measured vitamin B12, and 13 measured homocysteine. Nineteen out of 28 studies assessing folate reported significantly lower levels in pregnant women exposed to smoking compared with those unexposed. Vitamin B12 levels were lower in smoking mothers in eight out of 14 studies. Homocysteine levels tended to be higher in mothers exposed to smoking. Smoking exposure during pregnancy is generally associated with lower folate and vitamin B12 levels and higher homocysteine levels. This may help raise further awareness about the consequences of smoking and the need to encourage stopping smoking in all, especially in pregnant women.
| S-EPMC6585731 | biostudies-literature
Project description:Background & aimsMetabolic syndrome (MetS) is associated with life-threatening conditions. Several studies have reported an association of vitamin B12, folic acid, or homocysteine (Hcy) levels with MetS. This systematic review and meta-analysis assessed the association of vitamin B12, folic acid, and Hcy levels with MetS.MethodsPubMed, Scopus, Embase, Ovid/Medline, and Web of Science were searched up to February 13, 2023. Cross-sectional, case-control, or cohort studies were included. A random-effects model was performed using the DerSimonian and Laird method to estimate the between-study variance. Effect measures were expressed as odds ratios (OR) with their corresponding 95% confidence intervals (95% CI). Between-study heterogeneity was evaluated using Cochran's Q test and the I2 statistic.ResultsSixty-six articles (n = 87,988 patients) were included. Higher vitamin B12 levels were inversely associated with MetS (OR = 0.87; 95% CI: 0.81-0.93; p < 0.01; I2 = 90%). Higher Hcy levels were associated with MetS (OR = 1.19; 95% CI: 1.14-1.24; p < 0.01; I2 = 90%). Folate levels were not associated with MetS (OR = 0.83; 95% CI: 0.66-1.03; p = 0.09; I2 = 90%).ConclusionHigher vitamin B12 levels were inversely associated with MetS, whereas higher Hcy levels were associated with MetS. Studies assessing the pathways underlying this association are required.
| S-EPMC10527372 | biostudies-literature
Project description:Background: Studies on serum one-carbon metabolism factors (folate, B6, B12, homocysteine, and methionine) with lung cancer (LC) risk have produced inconsistent results. We aimed to systematically evaluate the association between them. Methods: This study was reported in accordance with the PRISMA Statement and was registered with PROSPERO (no. CRD42018086654). Relevant studies were searched in PubMed, Embase, MEDLINE, and CNKI up to February 2018. Random-effects models were used to estimate the pooled standardized mean differences (SMD) or odds ratios (OR), as well as their 95% confidence interval (CI). Sensitivity and subgroup analysis were performed to identify the source of heterogeneity. Publication bias was also assessed. Results: A total of 14 articles (8,097 patients) were included. The concentration of serum folate and vitamin B6 of LC patients were lower than the controls [SMD -0.53, 95% CI (-0.70, -0.35), p = 0.001 and SMD -0.28, 95%CI (-0.53, -0.02), p = 0.001, respectively]. While the concentration of homocysteine of the cases was higher than the controls [SMD 0.41, 95% CI (0.24, 0.59), p = 0.001]. However, there were no significant differences between LC patients and the controls in terms of vitamin B12 and methionine [SMD -0.09, 95% CI (-0.27, 0.09), p = 0.202 and SMD -0.13, 95% CI (-0.36, 0.10), p = 0.001]. Subgroup analysis showed that these results were more significant in Europe, Asia, former and current smokers, and the male population (p-value < 0.05). Conclusions: Serum folate and vitamin B6 might be protective factors against lung carcinogenesis and homocysteine could contribute to LC risk.
| S-EPMC6220054 | biostudies-literature