A gene variant in the Atp10d gene associates with atherosclerotic indices in Japanese elderly population.

BACKGROUND: ATP10D belongs to a subfamily of P-type ATPases implicated in phospholipids translocation from the exoplasmic to the cytoplasmic leaflet of cellular biological membrane. Previous genome-wide association study (GWAS) identified that a variant in Atp10d gene (rs2351791) associates with serum lipid profile and myocardial infarction. The objective of this study is to assess the effect of this variant on atherosclerosis in Japanese elderly population. METHOD: Consecutive autopsy cases registered in JG-SNP study were recruited (n = 1536). The samples were pathologically assessed for atherosclerosis using macroscopic examination of the formalin-fixed arteries, and coronary stenotic index (CSI), intracranial atherosclerotic index (ICAI) and pathological atherosclerotic index (PAI), which represent systemic arteries were calculated. The variant rs2351791 (G/T) in Atp10d gene was genotyped by Taqman genotyping assay and association determined. RESULT: Both CSI and ICAI were significantly higher in GG genotype than GT genotype and TT genotype (p = 0.003 and p = 0.001, respectively). Both associations remained significant in minor allele dominant model after adjusting for age, hypertension, diabetes, HDL, smoking and drinking (p = 0.001 and p = 0.001, respectively). PAI was not associated with this variant. Consistent with the previous report, plasma HDL cholesterol level was lower in GG genotype compared to GT + TT genotypes (p = 0.001). CONCLUSION: The rs2351791 SNP in the Atp10d gene affects the susceptibility for cardiac and intracranial vascular stenosis in the elderly Japanese population.

Association of COMT gene polymorphisms with systemic atherosclerosis in elderly Japanese.

AIM: Atherosclerotic disease is a major health problem among the elderly, which arises from a complex interaction between genetic and environmental factors. The catechol-O-methyltransferase (COMT) gene encodes an enzyme that degrades catecholamines and estrogens to less active metabolites. The objective of this study was to examine whether polymorphisms of the COMT gene affected the severity of atherosclerotic disease in a Japanese elderly population. METHOD: A total of 1536 autopsy cases of hospital deaths were assessed for the degree of pathological atherosclerotic index (PAI), coronary stenotic index (CSI) and intracranial stenotic index (ICAI), which were obtained by macroscopic examination of the luminal surface of formalin-fixed arteries. Two single nucleotide polymorphisms (SNPs) in the COMT gene, rs4633 (C/T) and rs4680 (G/A) were genotyped. The rs4680 (G/A) corresponds to a functional SNP with the substitution of valine to methionine. RESULT: The CC genotype of rs4633 (C/T) and the GG genotype of rs4680 (G/A) showed a significantly higher degree of PAI and the association remained positive after adjustment for age, hypertension, diabetes, smoking and drinking (p=0.035 and p=0.031, respectively). There were no significant associations between COMT genotypes and CSI or ICAI. When male and female subjects were analyzed separately, the association was observed only in female subjects (p=0.012 and p=0.027) after adjustment for age, hypertension, diabetes, smoking and drinking. CONCLUSION: The functional SNP in the COMT gene associated with the severity of atherosclerosis in a Japanese elderly population, whereby the influence of the genotype appears to be stronger in females than in males.