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香港华人肾素-血管紧张素系统基因多态性、血压、血脂异常与糖尿病:ACE插入/缺失多态性与2型糖尿病的显著关联。

Renin-angiotensin system gene polymorphisms, blood pressure, dyslipidemia, and diabetes in Hong Kong Chinese: a significant association of tne ACE insertion/deletion polymorphism with type 2 diabetes.

作者信息

Thomas G N, Tomlinson B, Chan J C, Sanderson J E, Cockram C S, Critchley J A

机构信息

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin.

出版信息

Diabetes Care. 2001 Feb;24(2):356-61. doi: 10.2337/diacare.24.2.356.

Abstract

OBJECTIVE

In Chinese populations, hypertension is common and is a major risk factor for cerebrovascular and coronary heart disease, particularly when associated with diabetes. The clustering of these disorders and dyslipidemia and obesity is termed the metabolic syndrome and is increasing in prevalence in the populations of modernizing Asian nations. The renin-angiotensin system (RAS) helps maintain blood pressure and salt homeostasis and may play a role in the pathogenesis of aspects of the metabolic syndrome. We investigated three RAS gene polymorphisms--the ACE insertion/deletion (I/D), angiotensinogen (AGT) M235T, and angiotensin II type 1 receptor (AT1R) A1166C polymorphisms--for a possible role in modulating these disorders in 853 Chinese subjects with varying components of the metabolic syndrome.

RESEARCH DESIGN AND METHODS

The three gene polymorphisms of this cross-sectional study were detected using polymerase chain reaction-based protocols. The genotype frequencies were compared between the controls (n = 119) and both overlapping and nonoverlapping groups of patients with type 2 diabetes, hypertension, and dyslipidemia using chi2 test. Differences in levels of the biochemical parameters between the genotypes were determined using analysis of variance.

RESULTS

No significant relationship was identified between these polymorphisms and blood pressure in this population. Although the AT1RA1166C polymorphism was not associated with any aspect of the metabolic syndrome examined, there was limited evidence to suggest that the AGT M235T polymorphism may be associated with cholesterol levels. The ACE I allele was significantly more frequent in each group comprising subjects with type 2 diabetes/glucose intolerance (GIT), and the I allele was associated with higher fasting plasma glucose levels.

CONCLUSIONS

These findings suggest that these polymorphisms are unlikely to be involved in the pathogenesis of hypertension. The ACE I/D polymorphism was associated with the metabolic syndrome, having a higher frequency of I allele-containing genotypes in those groups, but this appeared to result predominantly from the relationship with type 2 diabetes/GIT in this population of Chinese subjects.

摘要

目的

在中国人群中,高血压很常见,是脑血管病和冠心病的主要危险因素,尤其是与糖尿病并存时。这些疾病与血脂异常和肥胖聚集在一起被称为代谢综合征,在亚洲现代化国家的人群中患病率正在上升。肾素-血管紧张素系统(RAS)有助于维持血压和盐平衡,可能在代谢综合征某些方面的发病机制中起作用。我们在853名有不同代谢综合征组分的中国受试者中研究了三种RAS基因多态性——ACE插入/缺失(I/D)、血管紧张素原(AGT)M235T和血管紧张素II 1型受体(AT1R)A1166C多态性——在调节这些疾病方面的可能作用。

研究设计与方法

采用基于聚合酶链反应的方案检测这项横断面研究的三种基因多态性。使用卡方检验比较对照组(n = 119)与2型糖尿病、高血压和血脂异常患者的重叠组和非重叠组之间的基因型频率。使用方差分析确定基因型之间生化参数水平的差异。

结果

在该人群中未发现这些多态性与血压之间存在显著关系。虽然AT1R A1166C多态性与所检查的代谢综合征的任何方面均无关联,但有有限证据表明AGT M235T多态性可能与胆固醇水平有关。ACE I等位基因在每组2型糖尿病/葡萄糖耐量异常(GIT)受试者中显著更常见,且I等位基因与更高的空腹血糖水平相关。

结论

这些发现表明这些多态性不太可能参与高血压的发病机制。ACE I/D多态性与代谢综合征相关,在那些组中含I等位基因的基因型频率更高,但这似乎主要是由于在这群中国受试者中与2型糖尿病/GIT的关系所致。

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