神经前体细胞表达发育调控样蛋白4基因多态性与哈萨克族高血压病的关联研究

Association between rs4149601 polymorphism and essential hypertension in Kazakh

目的 研究神经前体细胞表达发育调控样蛋白4基因（NEDD4L）变异与哈萨克族高血压病的相关性.方法 采取以人群为基础的横断面病例-对照研究方法 .采用TaqMan PCR技术对rs4149601多态性在哈萨克族自然人群中（883例 男性375例,女性508例 高血压383例,对照500例）进行分型 分析该多态性与哈萨克族高血压病的相关性 然后联合分析rs4149601与既往采用直接测序法在本人群中发现的NEDD4L基因3个代表性变异位点（296921-296923delTTG,rs2288774和rs2288775）组成的单体型与哈萨克族高血压病的相关性.结果 （1）rs4149601多态性的基因型、等位基因的分布符合Hardy-Weinberg平衡,3个代表性多态位点与rs4149601多态性间未发现有意义的连锁不平衡（r2＜0.8＝ （2）rs4149601多态性的基因型、等位基因在高血压组、对照组分布差异无统计学意义 （3）在总体、男性中,rs4149601,296921-3delTTG,rs2288774和rs2288775四个多态位点组成的单体型在高血压组、血压正常组分布差异无统计学意义 在女性中,D-C-G-G（296921-3delTTG/rs2288774/rs2288775/rs4149601）单体型在高血压组的频率高于血压正常组,且差异有统计学意义（P=0.026）.结论 rs4149601多态性与哈萨克族高血压病不相关 D-C-G-G（296921-3delTTG/rs2288774/rs2288775/rs4149601）单体型可能是新疆哈萨克族人高血压病的易感因素.

Objective To investigate the association between a functional rs4149601 polymorphism of neural precursor cell expressed developmentally downregulated 4-like gene （NEDD4L）and essential hypertension in Kazakh. Methods In this population-based association study, the genotypes of rs4149601polymorphism were identified by TaqMan PGR in 883 subjects （male 375 383 hypertensives） and its distribution and relationship to hypertension were studied. The association between haplotype （ rs4149601,296921-296923delTTG, rs2288774 and rs2288775, the last three polymorphisms are representative variations identified from 94 Kazakh hypertensive individuals by screening the functional region of NEDD4L previously） and hypertension was also investigated. Results The genotype distribution of rs4149601 polymorphism was in Hardy-Weinberg equilibrium. The genotype distribution of rs4149601 polymorphism was similar between the essential hypertension patients and the control individuals （ all P 〉 0. 05 ）. In the haplotype-based case-control analysis, the distribution of the haplotypes was not significantly different between the case and the control individuals in total and in male subjects but the frequency of D-C-G-G （296921-3delTTG/rs2288774/rs2288775/ rs4149601 ）haplotype was significantly higher in hypertensive than in control individuals in female （ P = 0. 026 ）. Conclusion Our results suggested that D-C-G-G hyplotype of NEDD4L but not rs4149601 polymorphism was linked with hypertension in Kazakh.