423 ANDROGENS AND AGGRESSIVENESS DO NOT MEDIATE THE EFFECT OF THE Y CHROMOSOME ON CARDIOVASCULAR RISK

Abstract

Introduction: Men develop coronary artery disease (CAD) ∼10 years earlier than age-matched women at a ratio of 2:1. A major biological difference between the genders, possibly accounting for this “male disadvantage”, is the Y chromosome. Haplogroup I of the Y chromosome increases risk of CAD by ∼50%. We sought to investigate if “male-specific” phenotypes previously associated with CAD may explain this effect. Methodology: We examined whether various measures of aggression and/or androgens may account for the association between haplogroup I and cardiovascular risk. 11 Y chromosome polymorphisms were genotyped in 1940 men (GRAPHIC, YMCA1, YMCA2) and using phylogenetic analysis each subject was assigned one Y chromosome lineage. Age-adjusted linear regression and fixed-effect inverse-variance meta-analysis was used to examine the effect of haplogroup I on each phenotype. Results: Meta-analysis of 1940 men showed no statistical difference in BMI, blood-pressure, lipids, glucose or renal function between carriers of haplogroup I and all other haplogroups. There were no statistical differences in measures of aggression in age-adjusted meta-analysis of 998 men from YMCA1 and 2 (meta-analysis p = 0.092, p = 0.016, p = 0.155, p = 0.315 and p = 0.164 for physical aggression, verbal aggression, anger, hostility and total aggression, respectively) after correction for multiple testing. Haplogroup I was also not associated with circulating levels of androgens in 861 men from YMCA1 (p = 0.388, p = 0912, p = 0.665, for testosterone, androstendione and DHEA-S respectively). Conclusions: These results suggest that neither traditional cardiovascular risk factors nor traits typically perceived as “male-specific” are likely to account for the association between the Y chromosome and cardiovascular risk.