杀伤细胞免疫球蛋白样受体基因多态性与原发性高血压关系的病例对照研究

Association between polymorphisms of killer cell immunoglobulin-like receptor gene and the risk of essential hypertension： a case-control study

目的 探讨杀伤细胞免疫球蛋白样受体（KIR）基因多态性与原发性高血压的关联性.方法 以社区资料为基础,采用病例对照研究方法,分析按年龄±2岁、同性别1∶1匹配的205对原发性高血压患者（病例组）和正常对照（对照组）.应用PCR-SSP方法检测KIR基因,利用广义多因子降维模型（GMDR）和SAS 9.1软件分析数据.结果 KIR各基因频率在病例组和对照组间的差异无统计学意义（P＞0.05）.KIR基因型9（不携带KIR3DSl和2DS3）在病例组的携带率高于对照组,差异有统计学意义（P＜0.05）.GMDR显示,KIR2DS2和KIR2DS3两个基因的交互作用检验精确度最高（55.13％）,交叉验证一致性为10/10,P=0.054.多因素分析显示,在调整了BMI、吸烟、饮酒和高血压家族史后,KIR2DS2阳性而KIR2DS3阴性者患原发性高血压的危险增加（OR=2.555,95％CI：1.203- 5.429,P=0.015）;KIR2DS2阳性且KIR2DS3阳性者患原发性高血压的危险降低（OR=0.268,95％CI：0.088- 0.815,P=0.020）;KIR2DS2阴性且KIR2DS3阳性者与原发性高血压不存在关联关系（OR=1.602,95％CI：0.785- 3.266,P=0.195）,与KIR2DS2阴性且KIR2DS3阴性者相比较.调整BMI、吸烟、饮酒和高血压家族史后,KIR2DS2和KIR2DS3的交互作用与原发性高血压显著关联（OR=0.065,95％CI：0.013- 0.317,P=0.001）.无论是未调整或经多因素调整后,KIR各基因及基因型与高血压均不存在关联关系（P＞0.05）.结论 携带KIR2DS2而不携带KIR2DS3者,患原发性高血压的危险增加;同时携带KIR2DS2和KIR2DS3可减少原发性高血压的患病危险,两者的拮抗作用可能是原发性高血压的保护因素。

Objective To assess the association between killer cell immunoglobulin-like receptor （KIR） gene polymorphisms and the risk of hypertension in autoimmune mechanism.Methods We conducted a case-control study including 205 hypertensives and 205 controls matched with sex and age,from a community-based population.KIR genes of all subjects were genotyped by polymerase chain reaction with sequence-specific primers （PCR-SSP）.Conditional logistic regression model and generalized multifactor dimensionality reduction （GMDR） method were used to estimate the association among KIR gene polymorphisms and the risk of hypertension.Results The genotypic frequencies of KIRs were not significantly different between the hypertensives and the control groups （P〉0.05）.Among all the models of GMDR concerning the association between interactions of KIR genes and essential hypertension,the testing accuracy of the interaction between K/R2DS2 and KIR2DS3 was the highest （55.13%）,with cross-validation consistency as 10/10 （P=0.054）.Results from the conditional logistic regression showed that individuals with KIR2DS2 ＋：KIR2DS3-were significantly associated with an increased risk on hypertension （OR=2.555,95%CI：1.203-5.429,P=0.015）.However,individuals with KIR2DS2 ＋：KIR2DS3 ＋ were significantly associated with a reduced risk of hypertension （0R=0.268,95% CI：0.088-0.815,P=0.020）.Individuals with KIR2DS2-KIR2DS3 ＋ did not seem to be associated with the risk of hypertension （0R=1.602,95% C I：0.785-3.266,P=0.195）,when compared to the KIR2DS2-KIR2DS3-group.Interactions between KIR2DS2 and KIR2DS3 were significantly associated with the risk of hypertension,after adjusted for BMI,smoking,drinking and family history of hypertension （OR=0.065,95%CI：0.013-0.317,P=0.001）.Conclusion Individuals with KIR2DS2 and no KIR2DS3 were associated with the increased risk of hypertension.KIR2DS2 that coexisted with KIR2DS3 were associated with the reduced risk of hypertension.Antagonism between KIR2DS2 and KIR2DS3 might serve as a protect factor for hypertension.