Dataset Information

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

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

Keene Keith L KL Chen Wei-Min WM Chen Fang F Williams Stephen R SR Elkhatib Stacey D SD Hsu Fang-Chi FC Mychaleckyj Josyf C JC Doheny Kimberly F KF Pugh Elizabeth W EW Ling Hua H Laurie Cathy C CC Gogarten Stephanie M SM Madden Ebony B EB Worrall Bradford B BB Sale Michele M MM

Frontiers in public health 20140806

<h4>Background</h4>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.<h4>Methods</h4>Extensive ...[more]

PMID: 25147783

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Project description:PurposeThis study aimed to identify and quantify the association and investigate whether serum vitamin B12 alone or vitamin B12 combined with folate and plasma total homocysteine (tHcy) levels could be used to predict the risk of acute ischemic stroke.Materials and methodsThis retrospective case-control study was conducted in the Department of Neurology, First Affiliated Hospital of Chongqing Medical University. It included 259 inpatients experiencing their first-ever acute ischemic stroke and 259 age-matched, sex-matched healthy controls. Patients were categorized into groups based on the etiology of their stroke: large-artery atherosclerosis (LAAS, n = 126), cardio embolism (CEI, n = 35), small vessel disease (SVD, n = 89), stroke of other determined etiology (ODE, n = 5), and stroke of undetermined etiology (UDE, n = 4). The associations of serum vitamin B12, folate, and plasma tHcy levels with the risk of ischemic stroke were evaluated using multivariable logistic regression analysis. Receiver operator characteristic (ROC) curves were used to assess the diagnostic power of vitamin B12, folate, and tHcy levels for ischemic stroke.ResultsSerum vitamin B12 and folate levels were significantly lower in ischemic stroke patients compared to controls, while plasma tHcy levels were significantly higher. The first quartile of serum vitamin B12 levels was significantly associated with an increased risk of LAAS (aOR = 2.289, 95% CI = 1.098-4.770), SVD (aOR = 4.471, 95% CI = 1.110-4.945) and overall ischemic stroke (aOR = 3.216, 95% CI = 1.733-5.966). Similarly, the first quartile of serum folate levels was associated with an increased risk of LAAS (aOR = 3.480, 95% CI = 1.954-6.449), CEI (aOR = 2.809, 95% CI = 1.073-4.991), SVD (aOR = 5.376, 95% CI = 1.708-6.924), and overall ischemic stroke (aOR = 3.381, 95% CI = 1.535-7.449). The fourth quartile of tHcy levels was also significantly associated with an increased risk of LAAS (aOR = 2.946, 95% CI = 1.008-5.148), CEI (aOR = 2.212, 95% CI = 1.247-5.946), SVD (aOR = 2.957, 95% CI = 1.324-6.054), and overall ischemic stroke (aOR = 2.233, 95% CI = 1.586-4.592). For predicting different types of ischemic stroke, vitamin B12 alone demonstrated the best diagnostic value for SVD, evidenced by a sensitivity of 71.0% and negative predictive value of 90.3%, along with the highest positive likelihood ratio (+ LR) for SVD. Vitamin B12 + tHcy + folate are valuable in predicting different types of ischemic stroke, with the most significant effect observed in SVD, followed by LAAS, and the weakest predictive effect in CEI. Additionally, vitamin B12 alone in combination with other indicators, such as folate alone, tHcy alone, and folate + tHcy could reduce negative likelihood ratio (-LR) and improve + LR.ConclusionsVitamin B12 was an independent risk factor for acute ischemic stroke. The risk calculation model constructed with vitamin B12 + tHcy + folate had the greatest diagnostic value for SVD.

Dataset Information

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

Publications

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

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