Effects of the Y Chromosome on Cardiovascular Risk Factors in Japanese Men

Excess cardiovascular risk in men compared with women has been suggested to be partly explained by effects of the Y chromosome. However, inconsistent results have been reported on the Y chromosome's genetic influence on blood pressure and lipid levels. The purpose of the present study was to settle the question whether genetic variants of the Y chromosome influence cardiovascular risk factors using a large epidemiological cohort, the Suita study. Possible influences of the Y chromosome polymorphisms (Y chromosome Alu insertion polymorphism [YAP], M175 and SRY+465) on cardiovascular risk factors were assessed in 974 Japanese men. The frequency of the YAP(+) allele in our study sample was 0.31. The prevalence of hypertension tended to be higher in YAP(+) than in YAP(−) men, and this tendency was found to be stronger among men aged 65 years or older. Men with the YAP(+) genotype had higher levels of high density lipoprotein (HDL) cholesterol compared with those with the YAP(−) genotype, even after adjustment for age, body mass index, and daily ethanol and cigarette consumption (57.0±14.6 mg/dL vs. 54.2±14.2 mg/dL, nominal p=0.011, adjusted p=0.0062). However, these observed nominal associations disappeared after adjusting for multiple testing (Bonferroni). No association was detected between the YAP genotype and myocardial infarction. Similarly, none of the associations with M175 and SRY+465 attained significance when multiple testing was taken into account. In conclusion, Y chromosome polymorphisms (YAP, M175 and SRY+465) do not appear to be associated with cardiovascular risk factors in Japanese men. Studies using much larger sample sizes and/or additional independent samples will be required for definitive conclusions.