内皮素1基因多态性与原发性高血压的病例对照研究

为探讨重庆市某社区人群内皮素1(Endothelin-1,ET-1)基因G8002A,+138A/-两个位点基因多态性与原发性高血压(Essential hypertension,EH)的相关性,采用PCR-RFLP和PCR-SSP方法分别检测95名EH患者及150名血压正常者组(NT)的G8002A和+138A/-基因多态性.结果发现:在EH组中发现+138A/-位点基因型与舒张压相关(p=0.005),其中4A4A型舒张压比3A3A型高13 mmHg(p=0.005),比3A4A型高12 mmHg(p=0.04).将G8002A与+138A/-位点联合分析后发现舒张压在EH病人中GA4A4A型较其他几型平均高达近20 mmHg.呈显著相关性(p＜O.01).认为ET-1基因+138A/-的A插入型变异位点可能与重庆市EH人群的舒张压水平有关,GA4A4A基因型人群可能是EH患者血压升高的一个高危遗传因素.

Abstract：

Objective: To investigate the association of the polymorphism of G8002A and+138A/-of the Endothelin-1 gene with essential hypertension(EH)in a sub-population of Chongqing.Methods: A casecontrol study was conducted using PCR-RFLP and PCR-SSP techniques to explore the ET-1 gene G8002A and+138A/-polymorphism in 95 essential hypertensives(EH group)and 150 normotensives(NT group)of Chongqing.Result: In the EH group,+138A/-gene variants influenced diastolic blood pressure(DBP)(p=0.005),and DBP in individuals with 4A4A carriers of+138A/-was 13 mm Hg higher than that in3A3A carriers(p=0.005)and 12 mm Hg higher than that in 3A4A carriers(p=0.04).An analysis of combined genotypes of G8002A and+138A/-showed that the combined genotypes of GA4A4A had about20 mm Hg higher DBP than other combined genotypes in the EH group(p＜0.01)Conclusion:+138A/-polymorphism may be involved in the increasing DBP level in EH in Chongqing population and the GA4A4A genotype might be a genetic risk factor for blood pressure raising in hypertensives.     

内皮素1基因多态性与原发性高血压的病例对照研究

为探讨重庆市某社区人群内皮素1(Endothelin-1,ET-1)基因G8002A,+138A/-两个位点基因多态性与原发性高血压(Essential hypertension,EH)的相关性,采用PCR-RFLP和PCR-SSP方法分别检测95名EH患者及150名血压正常者组(NT)的G8002A和+138A/-基因多态性.结果发现:在EH组中发现+138A/-位点基因型与舒张压相关(p=0.005),其中4A4A型舒张压比3A3A型高13 mmHg(p=0.005),比3A4A型高12 mmHg(p=0.04).将G8002A与+138A/-位点联合分析后发现舒张压在EH病人中GA4A4A型较其他几型平均高达近20 mmHg,呈显著相关性(p0.01).认为ET-1基因+138A/-的A插入型变异位点可能与重庆市EH人群的舒张压水平有关,GA4A4A基因型人群可能是EH患者血压升高的一个高危遗传因素.     

ET-1+138A/-基因多态性与女性舒张压的相关性

目的:探讨重庆市地区人群血管内皮素1基因(Endothelin-1,ET-1)K198N,+138A/-位点基因多态性(Single nucleotide polymorphisms,SNP)与原发性高血压(EH)的相关性.方法:采用引物特异性片段长度多态性(PCR-SSP)法,检测95例原发性高血压患者及155例血压正常者ET-1基因的K198N,+138A/-位点多态性.并从中抽取36例高血压患者,40例血压正常者,用放射免疫法测定其血浆内皮素的浓度.结果:女性高血压中+138A/-多态性与舒张压有关(p=0.004),4A4A基因型舒张压比3A3A型高16 mmHg(p=0.004),较3A4A型高15 mmHg(p=0.035).将4A4A与3A4A型合并后其舒张压较3A3A型高(p=0.041).而在女性对照组以及男性中均无此关系.未发现K198N位点基因型与血压之间的相关性.结论:女性EH患者中,4A型携带者舒张压更容易升高,4A等位基因可能是女性EH患者血压升高的一个危险因素.进一步探讨其作用机制,可以为EH患者的个体化预防治疗提供依据.

Abstract：

Objective: To investigate the association between K198N, + 138A/- polymorphisms (SNP) of endothelin-1 (ET-1) gene and essential hypertension in a sub-population of Chongqing. Methods: Sequence-specific primer polymerase chain reaction (SSP-PCR) was used to detect the genetic polymorphisms of endothelin-1 (ET-1) gene in 95 hypertensive patients and 155 normotensive subjects. Plasma ET concentration was measured by radioimmunoassay in 36 hypertensive patients and 40 normotensive subjects.Result: +138A/-gene variants influenced diastolic blood pressure (DBP) only in female hypertensive (p=0. 004), DBP in female individuals with 4A4A carriers of +138A/- was 16mm Hg higher than that in 3A3A carriers(p=0. 041)and 15mm Hg higher than that in 3A4A carriers (p=0. 035). The above relationship was not found in the female control group and in the male groups and there was no relationship between K198N genotype and blood pressure. There was also no significant genotype-associated difference in plasma ET. Conclusion: Female hypertensive with 4A allele had a higher probability of having higher DBP; therefore 4A allele might be a risk factor for blood pressure rise in female hypertensive. Understanding this mechanism of action can further help to find new therapies for hypertensive patients, especially in the female population.     

内皮素1基因多态性与高血压缺血性卒中的关系

目的: 探讨ET-1基因的Lys198Asn和TaqI酶切两个多态性位点与高血压缺血性卒中的关系. 方法: 运用序列特异引物聚合酶链反应(sequence specific primer polymerase chain reaction, SSP-PCR)和限制性内切酶片段长度多态性(restriction fragment length polymorphism, RFLP)的方法了解46例原发性高血压(essential hypertension, EH)缺血性卒中的病人和50例EH未发生卒中的病人的Lys198Asn和TaqI酶切两个位点基因型分布情况. 结果: Lys198Asn和TaqI酶切位点多态性在对照组基因分布频率符合Hardy-Weinberg平衡. Lys198Asn基因型频率和等位基因频率在卒中组和对照组之间有统计学差异(p＜0.05), 基因型频率的相对风险分析发现, GT+TT基因型患卒中的风险是GG基因型的4.855倍. (OR=4.855, 95%CI: 2.197～16.608)TaqI酶切位点基因型分布频率在卒中组和对照组之间无统计学差异(p＞0.05), 等位基因频率有临界统计学差异(marginally significant)(p=0.04). 携带GG(Lys198Asn)+ GG(Taq I酶切多态性)基因型的患者发生高血压缺血性卒中的风险增加(p=0.035, OR=0.991, 95% CI=0.01～0.84). 结论: 人类ET-1基因的Lys198Asn位点T等位基因可能是人群发生高血压缺血性卒中的易感因素. TaqI酶切位点可能与其有协同作用.