Effect of a common X-linked angiotensin II type 2-receptor gene polymorphism (−1332 G/A) on the occurrence of premature myocardial infarction and stenotic atherosclerosis requiring revasculariz

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• 作者：K. Alfakih ; B. Brown ; R.A. Lawrance ; P. Warburton ; A. Maqbool ; K. Walters ; N.J. Samani ; S.G. Ball ; A.J. Balmforth ; A.S. Hall
• 关键词：Angiotensin ; Genetics ; Coronary disease ; Molecular biology
• 刊名：Atherosclerosis
• 出版年：2007
• 期刊代码：28_00219150
• 类别：med
• 出版时间：November 2007
• 卷：195
• 期：1
• 页码：e32-e38
• 文件大小：352 K

摘要

To assess the association of the angiotensin II type 2 (AT₂) receptor (−1332 G/A) gene polymorphism with premature coronary artery disease (CAD) and investigate for a further role in both myocardial infarction and predominantly stenotic atherosclerosis requiring revascularisation.

Methods and results

We investigated 885 families, which consisted of at least one sibling affected with premature CAD and at least one unaffected sibling. Genotyping of subjects was performed using a restriction enzyme digestion of an initial 310 bp PCR fragment that included the AT₂ (−1332 G/A) locus. The mean age of the 1143 individuals affected by premature CAD at the time of event was 50.6 ± 9.1 years. The genetic data were analyzed for these families using the X-linked sibling transmission disequilibrium test (XS-TDT). We observed significant evidence for an association for the AT₂ (−1332 G) locus and premature CAD (p-exact value = 0.028). This was driven by a highly significant result in men (p-exact value = 0.005). We performed further analyses to investigate for an association with myocardial infarction (Group 1) and stenotic atherosclerosis that was of sufficient severity as to require revascularization (Group 2). We found an increase in the frequency of the G/GG genotype in both Groups 1 and 2, being most marked in Group 2 (XS-TDT, p-exact value = 0.0134); logistic regression (p = 0.033, OR 1.38; 95%CI of 1.212–1.507).

Conclusion

We have observed evidence of association between the X-linked AT₂ (−1332 G/A) polymorphism and premature CAD with further evidence of a statistically significant association with stenotic atherosclerosis requiring revascularization.