Abstract 3194: A VAMP8 Gene Variant is Associated with Coronary Heart Disease in The Johns Hopkins Sibling Study
Background: We recently found that a variant of VAMP8, a gene involved in platelet degranulation, was associated with early-onset myocardial infarction (<63 years of age) in three case-control studies (a total of 821 cases and 1200 controls) of white individuals. In this study we asked if the VAMP8 variant was associated with coronary heart disease (CHD) in the Johns Hopkins Sibling and Family Heart Study, a study of black and white families with a history of CHD at a young age (<60 years).
Methods: A SNP in VAMP8 (rs1010) was genotyped in 246 patients with documented CHD and 401 unaffected siblings. The association of the prespecified risk allele (G) with CHD was analyzed in a generalized linear model that adjusted for race, sex, age and traditional risk factors including smoking, HDL-cholesterol, LDL-cholesterol, hypertension, and body mass index. The model also accounted for the relatedness of family members using generalized estimating equations.
Results: In a recessive model, the risk homozygotes had an odds ratio for CHD of 1.7 (CI, 1.1–2.8; P=0.03; homozygote frequency = 0.20). The risk estimates for CHD were similar in whites, blacks and male subgroups (see Figure⇓). We found no evidence for risk in the female subgroup (sex by genotype interaction P=0.28).
Conclusions: A VAMP8 gene variant showed a significant association with CHD in black and white families with a known history of premature CHD. These results suggest that, even for individuals with a known family history of disease, the VAMP8 gene variant may be a marker for CHD in males.