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Variation in the methylenetetrahydrofolate dehydrogenase 1‐like (MTHFD1L) gene and cardiovascular disease (CVD) risk
Author(s) -
Wernimont Susan M.,
Clark Andrew G.,
Stover Patrick J.,
Wells Martin T.,
Litonjua Augusto A.,
Weiss Scott T.,
Gaziano J. Michael,
Cassano Patricia A.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.724.16
Subject(s) - genotype , international hapmap project , linkage disequilibrium , single nucleotide polymorphism , genome wide association study , biology , genetics , genotyping , snp , locus (genetics) , medicine , gene
Two recent genome‐wide association (GWA) studies identified an intronic SNP (rs6922269) in a region of high linkage disequilibrium (LD) in the MTHFD1L gene that was associated with an increased heart disease risk. The present study explored joint genotypes across 6 variants in this LD block in relation to CVD using a nested case‐control design (378 cases, 425 noncases). OR and 95% CI for the joint genotypes were estimated with conditional logistic regression. In HapMap CEU data, certain joint genotypes were found to be unambiguous proxies for the rs6922269 and rs9767752 SNPs, thus these genotypes could be inferred. Participants with combinations that were unambiguous proxies for genotype rs6922269 AA had a 1.27‐fold increased CVD risk vs. genotype GG (95% CI 0.75, 2.1), a finding similar in magnitude to GWA findings, albeit with lower power. The rs9767752 SNP is proximal to an exon, and joint genotypes that were an unambiguous proxy for the CC genotype (vs. TT genotype) at this locus showed the strongest association with CVD (OR 2.28; 95% CI 1.0, 5.1). Joint genotypes representing the rs9767752 CT genotype were associated with a reduced CVD risk (0.79; 95% CI 0.5, 1.3). Overall the results serve as an adequate replication of association between variation in MTHFD1L and CVD. Funding: NIH T32 DK007158 ‐33 (SMW), G105 NHLBI Resequencing and Genotyping Service (PAC). Grant Funding Source NIH T32 DK007158 ‐33 (SMW)