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[盐敏感性高血压易感基因多态性的跨种族分析]

[A cross-racial analysis on the susceptible gene polymorphisms of salt-sensitive hypertension].

作者信息

Lu Jia-peng, Zhang Ling, Wang Wei

机构信息

Department of Epidemiology and Biostatistics, Capital Medical University, Beijing 100069, China.

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2010 Oct;38(10):943-8.

Abstract

OBJECTIVE

To compare the genetic distributions of salt-sensitivity of four ethnic populations in Hapmap database.

METHODS

The frequencies data (395 subjects) of salt-sensitivity polymorphisms (AGT/M235T, ACE/ID, CYP11B2/C-344T, ADDI/Gly460Trp, GNB3/C825 and CYP3A5/A6986G)of Utah residents with ancestry from northern and western Europe (CEU), Han Chinese in Beijing (CHB), Japanese in Tokyo (JPT) and Yoruba mother-father-child trios in Ibadan, Nigeria (YRI) were obtained from International HapMap Project. The good-fit χ(2) test was performed to test whether the frequencies of each genotype reached Hardy-Weinberg equilibrium. The differences of the genotype and allele distribution and trend analysis were detected via χ(2) test. Furthermore, multiple comparisons between two populations were analyzed by Lancaster's partition of chi-squares.

RESULTS

There were significant differences of each genotype distribution among four ethnic populations (P < 0.05). The distribution of genotype frequencies and susceptible allele frequencies of salt sensitive candidate genes were similar between CHB and JPT. Excepted for GNB3/825T allele (38.8% vs.34.4%, P = 0.521), susceptible allele frequencies in AGT/235T (79.2% vs. 41.2%, P < 0.001), ACE/I (56.5% vs. 43.5%, P < 0.001), CYP11B2/-344T (74.1% vs. 56.7%, P = 0.001), ADDI/460Trp (51.8% vs. 20.4%, P < 0.001) and CYP3A5/A6986 (30.1% vs. 3.6%, P < 0.001) were significantly higher in CHB than in CEU. There distribution of ADDI/460Trp allele was significant lower in YRI (4%) than in CHB (51.8%, P < 0.001). However frequencies of AGT/235T, CYP11B2/-334T, GNB3/825T and CYP3A5/6986A in CHB were significantly lower than those in YRI (P < 0.05). Trend analyses showed significantly increased trend in AGT/235T (41.2% < 79.2% < 92.0%, P < 0.001), CYP11B2/-334T (56.7% < 74.1% < 84.8%, P < 0.001) and CYP3A5/6986A (3.6% < 30.1% < 84.5%, P < 0.001) in CEU, CHB and YRI.

CONCLUSIONS

There are significant discrepancy of salt-sensitivity variant distributions among four ethnic populations in Hapmap database. The frequencies of the susceptible polymorphisms related to salt-sensitivity in Beijing Han population was similar with JPT, higher than in CEU but lower than in YRI, suggesting high salt-sensitive and risk for hypertension in Beijing Han population. Prevention and individual therapy for high-risk population will help to reduce the prevalence of salt-sensitive hypertension and cardiovascular diseases.

摘要

目的

比较Hapmap数据库中四个种族人群盐敏感性的基因分布情况。

方法

从国际Hapmap计划获取来自北欧和西欧的犹他居民(CEU)、北京汉族(CHB)、东京日本人(JPT)以及尼日利亚伊巴丹的约鲁巴父母子三人组(YRI)的盐敏感性多态性(AGT/M235T、ACE/ID、CYP11B2/C-344T、ADDI/Gly460Trp、GNB3/C825和CYP3A5/A6986G)的频率数据(395名受试者)。进行拟合优度χ(2)检验以检测每种基因型的频率是否达到哈迪-温伯格平衡。通过χ(2)检验检测基因型和等位基因分布的差异以及趋势分析。此外,通过兰开斯特卡方分割分析两个群体之间的多重比较。

结果

四个种族人群中每种基因型分布存在显著差异(P < 0.05)。CHB和JPT之间盐敏感候选基因的基因型频率和易感等位基因频率分布相似。除了GNB3/825T等位基因(38.8%对34.4%,P = 0.521),CHB中AGT/235T(79.2%对41.2%,P < 0.001)、ACE/I(56.5%对43.5%,P < 0.001)、CYP11B2/-344T(74.1%对56.7%,P = 0.001)、ADDI/460Trp(51.8%对20.4%,P < 0.001)和CYP3A5/A6986(30.1%对3.6%,P < 0.001)的易感等位基因频率显著高于CEU。YRI中ADDI/460Trp等位基因的分布(4%)显著低于CHB(51.8%,P < 0.001)。然而,CHB中AGT/235T、CYP11B2/-334T、GNB3/825T和CYP3A5/6986A的频率显著低于YRI(P < 0.05)。趋势分析显示,CEU、CHB和YRI中AGT/235T(41.2% < 79.2% < 92.0%,P < 0.001)、CYP11B2/-334T(56.7% < 74.1% < 84.8%,P < 0.001)和CYP3A5/6986A(3.6% < 30.1% < 84.5%,P < 0.001)有显著增加趋势。

结论

Hapmap数据库中四个种族人群盐敏感性变异分布存在显著差异。北京汉族人群中与盐敏感性相关的易感多态性频率与JPT相似,高于CEU但低于YRI,提示北京汉族人群盐敏感性高且患高血压风险高。对高危人群进行预防和个体化治疗将有助于降低盐敏感性高血压和心血管疾病的患病率。

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