HSG基因单核苷酸多态性与原发性高血压的相关性研究

Relationship of the HSG gene single nucleotide polymorphism and hypertension

目的通过研究不同人群中新发现的增殖抑制基因HSG基因多态性,揭示增殖抑制基因多态性与高血压的关系。方法2002年4月至2003年9月选取原发性高血压患者51例,男27例,女24例,平均年龄(57±8)岁;有高血压家族史的患者20例,女11例,男9例,平均年龄(38±22)。74名健康对照,男38例,女36例,平均年龄(54±8)岁。取外周静脉血并提取DNA,设计相应的引物,PCR扩增法获得相应的产物,应用DNA测序法直接得到PCR产物的核苷酸序列后比较不同人群相同片段的碱基组成及其特征。结果高血压组血清肌酐(CRE)和尿素氮(BUN)含量明显高于血压正常组,而高血压组和有高血压家族史组的收缩压和舒张压均明显高于血压正常组。HSG基因第12位内含子存在着3种突变(1q82139G/A、82153C/G、82273G/),其中后两种单核苷酸变异在高血压与健康人之间存在着明显差异,高血压家族史者与健康人比较也存在明显差异。不同人群中1q82139G/A无明显差异,且在人群中以CC基因型分布较为常见,G点删除更常见于有原发性高血压家族史的人群。结论肾功能的指标(CRE和BUN)可能可以较早地反映高血压的进展和靶器官损害的状态。HSG基因第12位内含子存在着3种突变1q82139G/A、82153C/G和82273G/,其中1q82139G/A可能是一种无义突变。

Objective To investigate the single nucleotide polymorphism (SNP) of the novel hyperplasia suppressor gene (HSG) to uncover the relationship between HSG SNP and hypertension.Methods Totally, 74 normotensive people (38 men and 36 women), 51 patients with essential hypertension (27 men and 24 women) and 20 hypertensive patients with family history of essential hypertension (9 men and 11 women) were chosen, with mean ages of (54 ± 8) years, (57± 8)years and (38 ± 22) years, respectively. Peripheral venous blood specimen was collected from each of them and then DNA was extraced. The right primers were designed for DNA amplification with PCR. Each of the PCR-products from different groups was sequenced by ABI PRISM 377-DNA sequencer and their base components and characteristics of the same fragment were compared each other.Results Blood levels of creatinine (CRE) and urea nitrogen (BUN) were significantly higher in the hypertensives than in the normotensives (P<0.01). Systolic and diastolic blood pressures were significantly higher in the hyperteensives and the hypertensives with family history of essential hypertension than in the normotensives (P<0.01 and P<0.05). There existed three kinds of SNP in the HSG 12th intron (1q82139 G/A, 82153C/G and 82273G/-), and there was significant difference in 1q82153C/G and 82273G/-SNP between the hypertensives and normotensives (P<0.05 and P<0.01) and between the hypertensives with family history and the normrtensives (P<0.01 and P<0.01). And, the similar difference in C/G allele and G deletion could be found in different populations. Moreover, the CC genetype of 1q82153 was common in the population (P<0.01) and G deletion was more common in Chinese Han people with family history of essential hypertension. There was no significant difference existed in 1q82139 G/A mutation among the three groups.Conclusions Measurements of renal function indicators (CRE and BUN) could probably reflect earlier advance of hypertension and damage to target organs. There existed three kinds of mutation in the ~12th intron of the HSG 1q82139 G/A, 82153 C/G and 82273 G/-. The 1q82139 G/A could be a nonsense mutation and there was significant difference in the 1q82153 C/G and 1q82273 G/-SNP and gene frequencies between different Chinese Han populations, which could be independent risk factors for essential hypertension.