The clinical significance of a common, functional, X-linked angiotensin II type 2-receptor gene polymorphism (−1332 G/A) in a cohort of 509 families with premature coronary artery disease

AIMS: To assess, in families with premature coronary artery disease (CAD), the possible association, with linkage, of the X-linked AT2 receptor (-1332 G/A) gene polymorphism and premature CAD. METHODS AND RESULTS: We investigated 509 families with a history of premature CAD that consisted of one sibling affected with premature CAD and two unaffected siblings. Genotyping of subjects was performed using a restriction enzyme digestion of an initial 310 bp polymerase chain reaction fragment that included the AT2 (-1332 G/A) locus. The mean age of the 611 individuals affected by premature CAD at the time of event was 49.5 +/- 8.1 years. Conditional logistic regression analysis confirmed a significant predictive value of premature CAD for the covariates of hypertension, diabetes, dyslipidaemia, history of smoking, and male gender. The genetic data were analysed for these families using the X-linked sibling transmission/deletion test (XS-TDT) statistics program. In hemizygous men we observed evidence for association in the presence of linkage, for the AT2 (-1332 G/A) locus and premature CAD (P-exact value = 0.024) and also a trend towards association, in the presence of linkage, for this polymorphism and hypertension (P-exact value = 0.08). CONCLUSIONS: We have observed evidence of association between the presence of linkage for the X-linked AT2 (-1332 G/A) polymorphism and premature CAD in hemizygous males.