内皮型一氧化氮合酶基因Glu298Asp多态性与原发性高血压的关系

目的探讨中国大连人群eNOs基因Glu298Asp多态性与原发性高血压的关系。方法选取277名高血压患者及547名血压正常者,提取基因组DNA,使用聚合酶链反应(PCR)及限制性片段长度多态性(RFLP)分析确定eNOs Glu298Asp多态性。进行两组问的比较并使用Logistic,回归分析年龄、性别、家族史、TC、TG、BMI及基因型对高血压的影响。结果基因型频率及等位基因频率在高血压和对照组的分布无差异。高血压组氨基酸298位GG、GT、TT基因型频率分别为84．1％、14．4％、1．4％,在对照组为85．6％、13．5％、0．9％(P=O．73)。Asp等位基因的频率在高血压组及对照组分别为8．7％和7．7％,(P=0．50)。对年龄、性别和BMI及有无家族史进行亚组分析也未发现基因型的分布在各组间有差异。采用隐性遗传模型把GG和GT基因型合并,GG GT和TT基因型的分布在两组间仍未发现有显著差异(P=0．49)。Logistic回归显示年龄、BMI、家族史及饮酒是高血压发病的独立危险因素,OR值分别为1．09(P<0．001)、1．28(P<0．001)、9．53(P<0．001)和2．26(P<0．05)。结论本实验显示年龄、BMI、家族史及饮酒是高血压的独立危险因素。eNOs基因Glu298Asp突变可能不是大连人原发性高血压的主要易感基因。

Relationship between the Glu298Asp Polymorphism of the Endothelial Nitric Oxide Synthase Gene and Essential Hypertension

Objective To clarify the uncertain picture about the relationship of the Glu298Asp polymorphism of the eNOs gene with EH by conducting a case-control study of a relatively large group. Methods 277 patients with essential hypertension were selected from the outpatient clinics at the Second Affiliated Hospital of Dalian Medical University. Genomic DNA was extracted . The eNOs Glu298As polymorphism was detected by using polymerase chain reaction (PCR) and restriction fragment-length polymorphism (RFLP) analysis. Results No significant difference was observed in the comparison of either genotype distribution or allele frequencies between hypertensive and normotensive groups. The frequencies of GG, GT, and TT genotypes at amino acid 298 were 84. 1% , 14.4% , 1.4% in hypertensive subjects and 85. 6% , 13. 5% , 0. 9% in normotensive subjects (P = 0. 73) . The frequencies of the Asp allele were 8. 7% and 7.7% , respectively (P = 0. 50). We analyzed the data by stratifying patients and control subjects according to age ,gender and BMI . Difference in the genotype distributions was also not seen. In addition, no significant difference was found when a subgroup of hypertensives having family history of hypertension was compared with the controls without family history (P = 0. 25) . When we assumed a recessive model of inheritance and the GG and GT genotype were combined and compared with the TT genotype, No significant difference was observed in the comparison of genotype (GG GT versus TT) distribution between hypertensive and normotensive groups (P = 0. 49). Logistic regression was used to assess interactions between age, sex, family history of hypertension, TC, TG and BMI and the eNOs genotypes. Age, BMI, family history of hypertension and alcohol intake are independent risk factors of hypertension. The OR are 1. 09 (P < 0 . 001) , 1. 28 (P < 0. 001) , 9. 53 (P<0.001) and 2.26 (P<0. 05) respectively. Conclusions In summary, our data supporting body mass index (BMI) , age, family history and alcohol intake are independent risk factors for essential hypertension. And our data suggest that the eNOs Glu298Asp variant is not a major risk factor for essential hypertension in Dalian.