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.
OBJECTIVE
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.


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.
Alfakih
Khaled
K
BHF Heart Research Centre (Clinical), G Floor, Jubilee Wing, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK.
Lawrance
Richard A
RA
Maqbool
Azhar
A
Walters
Kevin
K
Ball
Stephen G
SG
Balmforth
Anthony J
AJ
Hall
Alistair S
AS
D017668:Age of Onset; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003327:Coronary Disease / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications; D006973:Hypertension / Q000150:complications; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects
D044139:Receptor, Angiotensin, Type 2