E-选择素基因多态性与原发性高血压相关：一项中国人群的病例对照初步研究。

E-selectin gene polymorphisms are associated with essential hypertension: a case-control pilot study in a Chinese population.

机构信息

Department of Hypertension, Beijing Anzhen Hospital, Attached to Capital University of Medical Sciences, Beijing Institute of Heart, Lung, Blood Vessel Diseases, Beijing, 100029, China.

出版信息

BMC Med Genet. 2010 Aug 27;11:127. doi: 10.1186/1471-2350-11-127.

DOI:10.1186/1471-2350-11-127

PMID:20796317

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2940768/

Abstract

BACKGROUND

Genetic variation is thought to contribute to the etiology of hypertension, and E-selectin is a candidate essential hypertension-associated gene. This study thus sought to investigate possible genetic associations between the T1880C, C602A and T1559C polymorphisms of E-selectin and essential hypertension.

METHODS

Hypertensive patients (n = 490) and healthy normotensive subjects (n = 495) were screened for the genotypes T1880C, C602A and T1559C using real-time quantitative polymerase chain reaction after DNA extraction to identify representative variations in the E-selectin gene. The associations between genotypes and alleles of the three mutations and essential hypertension were then analyzed using a case-control study.

RESULTS

Hypertensive patients and normotensive subjects were significantly different with respect to the genotypes CC, CA and AA (P = 0.005) and the C-allele frequency of C602A (P = 0.001). A comparison of dominant versus recessive models also revealed significant differences between the two groups (P = 0.004 and P = 0.02). When subgrouped by gender, these indexes differed significantly between normotensive and essential hypertensive males, but not in females. The additive model of the T1559C genotype did not differ between essential hypertensive and normotensive groups overall (P = 0.39), but it was different between hypertensive and normotensive males (P = 0.046) and females (P = 0.045). The CC + TC versus TT frequency of T1559C was also different in the recessive model of male hypertensive and normotensive groups (P = 0.02). Further analysis showed that C602A and T1559C were significantly associated with hypertension (C602A: OR = 7.58, 95%CI = 1.53-11.97, P < 0.01; and T1559C: OR = 6.77, 95%CI = 1.07-1.83, P < 0.05). The frequency of the C-C-C haplotype was significantly higher in hypertensive patients than in control individuals as well as in hypertensive and normotensive males (P = 0.008 and 0.01). The frequency of the C-A-T haplotype was higher only in male hypertensives and normotensives (P = 0.015). Furthermore, there was a significant interaction between E-selectin and gender (P = 0.02 for C602A and 0.04 for T1559C).

CONCLUSION

C602A and T1559C may be independent risk factors for essential hypertension in the Chinese population, whereas T1880C is not.

摘要

背景

遗传变异被认为是导致高血压的病因之一，E-选择素是原发性高血压相关基因的候选基因。因此，本研究旨在探讨 E-选择素基因 T1880C、C602A 和 T1559C 多态性与原发性高血压之间可能存在的遗传关联。

方法

通过实时定量聚合酶链反应（PCR）在 DNA 提取后，筛选高血压患者（n=490）和健康血压正常对照者（n=495）的 T1880C、C602A 和 T1559C 基因型，以鉴定 E-选择素基因中的代表性变异。然后，采用病例对照研究分析三种突变的基因型和等位基因与原发性高血压之间的关联。

结果

高血压患者和血压正常对照者在 CC、CA 和 AA 基因型（P=0.005）和 C602A 等位基因频率（P=0.001）方面存在显著差异。显性与隐性模型的比较也显示两组之间存在显著差异（P=0.004 和 P=0.02）。按性别亚组分析，这些指标在男性血压正常对照者和原发性高血压患者之间存在显著差异，但在女性中没有差异。T1559C 基因型的加性模型在原发性高血压患者和血压正常对照者之间总体上没有差异（P=0.39），但在男性高血压患者和血压正常对照者（P=0.046）和女性（P=0.045）之间存在差异。T1559C 的 CC+TC 与 TT 频率在男性高血压患者和血压正常对照者的隐性模型中也存在差异（P=0.02）。进一步分析表明，C602A 和 T1559C 与高血压显著相关（C602A：OR=7.58，95%CI=1.53-11.97，P<0.01；T1559C：OR=6.77，95%CI=1.07-1.83，P<0.05）。高血压患者的 C-C-C 单倍型频率明显高于对照组和高血压及血压正常男性（P=0.008 和 0.01）。仅在男性高血压患者和血压正常对照者中，C-A-T 单倍型频率较高（P=0.015）。此外，E-选择素与性别之间存在显著的交互作用（P=0.02 用于 C602A 和 0.04 用于 T1559C）。