Dataset Information

Genetic polymorphism rs6922269 in the MTHFD1L gene is associated with survival and baseline active vitamin B12 levels in post-acute coronary syndromes patients.

ABSTRACT:

Background and aims

The methylene-tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L) gene is involved in mitochondrial tetrahydrofolate metabolism. Polymorphisms in MTHFD1L, including rs6922269, have been implicated in risk for coronary artery disease (CAD). We investigated the association between rs6922269 and known metabolic risk factors and survival in two independent cohorts of coronary heart disease patients.

Methods and results

DNA and plasma from 1940 patients with acute coronary syndromes were collected a median of 32 days after index hospital admission (Coronary Disease Cohort Study, CDCS). Samples from a validation cohort of 842 patients post-myocardial infarction (PMI) were taken 24-96 hours after hospitalization. DNA samples were genotyped for rs6922269, using a TaqMan assay. Homocysteine and active vitamin B12 were measured by immunoassay in baseline CDCS plasma samples, but not PMI plasma. All cause mortality was documented over follow-up of 4.1 (CDCS) and 8.8 (PMI) years, respectively. rs6922269 genotype frequencies were AA n = 135, 7.0%; GA n = 785, 40.5% and GG n = 1020, 52.5% in the CDCS and similar in the PMI cohort. CDCS patients with AA genotype for rs6922269 had lower levels of co-variate adjusted baseline plasma active vitamin B12 (p = 0.017) and poorer survival than patients with GG or GA genotype (mortality: AA 19.6%, GA 12.0%, GG 11.6%; p = 0.007). In multivariate analysis, rs6922269 genotype predicted survival, independent of established covariate predictors (p = 0.03). However the association between genotype and survival was not validated in the PMI cohort.

Conclusion

MTHFD1L rs6922269 genotype is associated with active vitamin B12 levels at baseline and may be a marker of prognostic risk in patients with established coronary heart disease.

SUBMITTER: Palmer BR

PROVIDER: S-EPMC3949666 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Genetic polymorphism rs6922269 in the MTHFD1L gene is associated with survival and baseline active vitamin B12 levels in post-acute coronary syndromes patients.

Palmer Barry R BR Slow Sandy S Ellis Katrina L KL Pilbrow Anna P AP Skelton Lorraine L Frampton Chris M CM Palmer Suetonia C SC Troughton Richard W RW Yandle Tim G TG Doughty Rob N RN Whalley Gillian A GA Lever Michael M George Peter M PM Chambers Stephen T ST Ellis Chris C Richards A Mark AM Cameron Vicky A VA

PloS one 20140311 3

<h4>Background and aims</h4>The methylene-tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L) gene is involved in mitochondrial tetrahydrofolate metabolism. Polymorphisms in MTHFD1L, including rs6922269, have been implicated in risk for coronary artery disease (CAD). We investigated the association between rs6922269 and known metabolic risk factors and survival in two independent cohorts of coronary heart disease patients.<h4>Methods and results</h4>DNA and plasma from 1940 patient ...[more]

PMID: 24618918

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Project description:BackgroundAgeing is characterised by physiological changes that can affect the nutrient availability and requirements. In particular, the status of vitamin D, cobalamin and folate has often been found to be critical in older people living in residential care. However, there is a lack of studies investigating the status of these nutrients in healthy and active home-dwelling elderly people.MethodsThe aim of this cross-sectional study was to assess the status of vitamin D based on serum concentrations of 25-hydroxycholecalciferol [25-(OH)D], cobalamin based on serum concentrations of holotranscobalamin (holoTC) and folate based on red blood cell (RBC) folate in unsupplemented, healthy and active German home-dwelling subjects ≥ 70 years of age (n = 134, mean ± SD: 75.8 ± 4.5 years). Dietary intake was assessed by 3-day food recalls. The study was conducted between March and November of 2021 (during the COVID-19 pandemic).ResultsThe mean 25-(OH)D concentration was high at 85.1 ± 26.0 nmol/L, while the majority of women (92%) and men (94%) had 25-(OH)D concentrations ≥ 50 nmol/L. Less than 10% of men and women had 25-(OH)D concentrations < 50 nmol/L. The mean holoTC concentration was 88.9 ± 33.7 pmol/L (94.8 ± 34.6 pmol/L in women and 73.6 ± 25.6 in men). Only 8% of the women were cobalamin deficient (< 50 pmol/L holoTC) compared to 22% of the men. The mean RBC folate concentration was 831 ± 244 nmol/L, while the prevalence of folate deficiency was 10%. Linear regression analysis showed that only folate equivalent intake was associated with the relevant nutrient status marker.ConclusionOur findings suggest that healthy, independently living older people with high levels of education, physical activity, and health awareness are not necessarily at higher risk of vitamin D, folate and cobalamin deficiency. Further studies are needed to verify these findings and to identify lifestyle and dietary patterns that can predict adequate nutrient status for healthy ageing.Trial registrationThis study is officially recorded in the German Clinical Trials Register (DRKS00021302).

Project description:Abstract Objectives Background: The FUT2 gene is responsible for the secretion of ABO blood type antigens into the body fluids (saliva, mucous, urine, tears, breast milk, sweat, and semen). Those who secrete the antigens into body fluids are call secretors, those who do not are called non-secretors. Hypothesis: GWAS studies have reported FUT gene variants to be associated with circulating vitamin-B12 (Vit-B12) concentrations. Missense mutations in the FUT2 gene result in a non-secretor phenotype. Thus, the secretory status of an individual may affect circulating vitamin-B12 concentrations over and above the genotype. Methods Materials and Methods: We included 780 participants (271 children, 282 mothers, and 227 fathers) from Pune Maternal Nutrition Study (PMNS). We measured the secretor status of individuals in saliva by hemagglutination test. A total of eight genetic variants including six SNPs from the FUT2 gene (rs492602, rs681343, rs281377, rs601338, rs1800027, and rs602662) and two SNPs from the FUT6 gene (rs3760776 and rs3760775) from our previous GWAS study were correlated with circulating vitamin-B12 levels. We tested the associations of FUT gene variants with secretor status phenotype and of the secretor phenotype with circulating vit-B12, folate, and ferritin concentrations in addition to H.pylori antibody levels. Results Results and Discussion: We found 33% of participants were non-secretors compared to 20% reported in Western Caucasian populations. Non-secretors had higher vitamin-B12 concentrations but not of folate and ferritin, vitamin-B12 associations were over and above FUT genotypes. Non-secretors showed a higher response to Vit-B12 supplementation. We found a FUT2 haplotype () to be strongly associated with Vit-B12 concentrations and non-secretor status. Non-secretors had lower H.pylori antibody concentrations. FUT6 genotype and haplotype were associated with Vit-B12 concentrations but not with secretor status and H.pylori antibody levels. Conclusions Our data suggest that secretor status may influence Vit-B12 concentrations through susceptibility to H.pylori infection and possibly other gut microbiota. A higher frequency of non-secretors in Indians could offer a selective advantage against Vit-B12 deficiency. Funding Sources BBSRC, UK; MRC, UK; WELLCOME TRUST, UK; DBT, India; ICMR India

Dataset Information

Genetic polymorphism rs6922269 in the MTHFD1L gene is associated with survival and baseline active vitamin B12 levels in post-acute coronary syndromes patients.

Background and aims

Methods and results

Conclusion

Publications

Genetic polymorphism rs6922269 in the MTHFD1L gene is associated with survival and baseline active vitamin B12 levels in post-acute coronary syndromes patients.

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