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肾素-血管紧张素-醛固酮系统(ACE、CYP11B2、AGTR1)中的多个多态性及其在多民族队列中对非裔美国人和拉丁裔高血压的影响。

Multiple Polymorphisms in the renin- angiotensin-aldosterone system (ACE, CYP11B2, AGTR1) and their contribution to hypertension in African Americans and Latinos in the multiethnic cohort.

作者信息

Henderson Sean O, Haiman Christopher A, Mack Wendy

机构信息

Department of Emergency Medicine, Keck School of Medicine, University of Southern California Los Angeles, CA 90033, USA.

出版信息

Am J Med Sci. 2004 Nov;328(5):266-73. doi: 10.1097/00000441-200411000-00006.

DOI:10.1097/00000441-200411000-00006
PMID:15545843
Abstract

OBJECTIVE

When compared with other U.S. populations, African Americans have excess hypertension. Genetic variants in elements of the renin-angiotensin-aldosterone system (RAAS), namely the angiotensin-converting enzyme (ACE), aldosterone synthase (CYP11B2), and angiotensin II type 1 receptor (AGTR1) genes, have been associated with risk of hypertension in some populations.

METHODS

We genotyped the D/I polymorphism in the ACE gene, the C(-344)T polymorphism in the CYP11B2 gene, and the C(-535)T polymorphism in the AGTR1 gene among African American and Latino members of the Multiethnic Cohort Study (MEC) to determine their association with hypertension.

RESULTS

We observed no significant increase in the risk of hypertension for either African Americans or Latinos homozygous or heterozygous for the D allele of the ACE gene. Among African Americans we observed carriers of the (-344)T allele of CYP11B2 to be at increased risk of hypertension (versus CC genotype: TC genotype, OR = 1.66 [95% CI: 1.01-2.72]; TT genotype, OR = 1.74 [95% CI: 1.07-2.82]). There was also an increase in risk of hypertension associated with the AGTR1 T allele for African Americans (versus CC genotype: TC genotype, OR = 2.62 [95% CI: 1.46-4.72]; TT genotype, OR = 2.67 [95% CI: 1.51-4.74]). The associations observed with CYP11B2 and AGTR1 genotypes were not observed among Latinos.

CONCLUSION

These data suggest that the (-535)T allele of AGTR1 and (-344)T allele of CYP11B2 may increase hypertension risk among African Americans but not among Latinos. Characterization of the linkage disequilibrium and haplotype patterns in the RAAS pathway genes will be crucial to understanding differences in hypertension susceptibility in these ethnic populations.

摘要

目的

与其他美国人群相比,非裔美国人患高血压的比例更高。肾素 - 血管紧张素 - 醛固酮系统(RAAS)相关基因变异,即血管紧张素转换酶(ACE)、醛固酮合酶(CYP11B2)和血管紧张素II 1型受体(AGTR1)基因,在某些人群中与高血压风险相关。

方法

我们对多民族队列研究(MEC)中的非裔美国人和拉丁裔成员的ACE基因D/I多态性、CYP11B2基因C(-344)T多态性和AGTR1基因C(-535)T多态性进行基因分型,以确定它们与高血压的关联。

结果

我们发现,ACE基因D等位基因纯合或杂合的非裔美国人和拉丁裔患高血压风险均未显著增加。在非裔美国人中,我们观察到CYP11B2基因(-344)T等位基因携带者患高血压的风险增加(与CC基因型相比:TC基因型,OR = 1.66 [95% CI:1.01 - 2.72];TT基因型,OR = 1.74 [95% CI:1.07 - 2.82])。非裔美国人中与AGTR1基因T等位基因相关的高血压风险也有所增加(与CC基因型相比:TC基因型,OR = 2.62 [95% CI:1.46 - 4.72];TT基因型,OR = 2.67 [95% CI:1.51 - 4.74])。在拉丁裔中未观察到与CYP11B2和AGTR1基因型相关的关联。

结论

这些数据表明,AGTR1基因的(-535)T等位基因和CYP11B2基因的(-344)T等位基因可能会增加非裔美国人患高血压的风险,但不会增加拉丁裔的风险。RAAS途径基因中连锁不平衡和单倍型模式的特征对于理解这些种族人群高血压易感性的差异至关重要。

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