Genetic Associations with Plasma B12, B6, and Folate Levels in an Ischemic Stroke Population from the Vitamin Intervention for Stroke Prevention (VISP) Trial.

ABSTRACT: BACKGROUND:B vitamins play an important role in homocysteine metabolism, with vitamin deficiencies resulting in increased levels of homocysteine and increased risk for stroke. We performed a genome-wide association study (GWAS) in 2,100 stroke patients from the Vitamin Intervention for Stroke Prevention (VISP) trial, a clinical trial designed to determine whether the daily intake of high-dose folic acid, vitamins B6, and B12 reduce recurrent cerebral infarction. METHODS:Extensive quality control (QC) measures resulted in a total of 737,081 SNPs for analysis. Genome-wide association analyses for baseline quantitative measures of folate, Vitamins B12, and B6 were completed using linear regression approaches, implemented in PLINK. RESULTS:Six associations met or exceeded genome-wide significance (P???5?×?10(-08)). For baseline Vitamin B12, the strongest association was observed with a non-synonymous SNP (nsSNP) located in the CUBN gene (P?=?1.76?×?10(-13)). Two additional CUBN intronic SNPs demonstrated strong associations with B12 (P?=?2.92?×?10(-10) and 4.11?×?10(-10)), while a second nsSNP, located in the TCN1 gene, also reached genome-wide significance (P?=?5.14?×?10(-11)). For baseline measures of Vitamin B6, we identified genome-wide significant associations for SNPs at the ALPL locus (rs1697421; P?=?7.06?×?10(-10) and rs1780316; P?=?2.25?×?10(-08)). In addition to the six genome-wide significant associations, nine SNPs (two for Vitamin B6, six for Vitamin B12, and one for folate measures) provided suggestive evidence for association (P???10(-07)). CONCLUSION:Our GWAS study has identified six genome-wide significant associations, nine suggestive associations, and successfully replicated 5 of 16 SNPs previously reported to be associated with measures of B vitamins. The six genome-wide significant associations are located in gene regions that have shown previous associations with measures of B vitamins; however, four of the nine suggestive associations represent novel finding and warrant further investigation in additional populations.

SUBMITTER: Keene KL 

PROVIDER: S-EPMC4123605 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature