European Heart Journal Advance Access originally published online on December 1, 2004
European Heart Journal 2005 26(6):584-589; doi:10.1093/eurheartj/ehi013
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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
1BHF Heart Research Centre (Clinical), G Floor, Jubilee Wing, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK
2BHF Heart Research Centre (Laboratory), Jubilee Wing, University of Leeds, Great George Street, Leeds LS2 9JT, UK
Received 20 March 2004; revised 12 September 2004; accepted 16 September 2004; online publish-ahead-of-print 1 December 2004.
* Corresponding author. Tel: +44 113 392 5393; fax: +44 113 392 5405. E-mail address: cvsash{at}leeds.ac.uk
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.
Key Words: Angiotensin • Genetics • Coronary disease • Molecular biology
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