【摘要】 目的筛查新疆阜康牧区哈萨克族原发性高血压人群NEDD4L基因变异位点。方法随机选择94例30~60岁高血压患者,利用美国AB I公司3100xl基因分析仪对NEDD4L编码区31个外显子、部分内含子以及转录起始点上游约500bp范围内的区域直接测序筛查该基因变异位点;并采用SNPalyzer软件分析变异位点间的连锁不平衡关系。结果共检出11个变异位点,除了位于第6内含子区的271420T>C(rs2288774)、271454A>G(rs2288775)变异与NCB I数据库中报道一致外,其余9个均为新发现的变异位点;在筛查出的11个变异位点中,rs2288774、rs2288775和296921-3delTTG为高频率SNPs,其余为低频率SNPs或稀有突变,没有发现错义突变;11个变异位点无连锁不平衡关系(r2<0.5)。结论本研究共检出11个变异位点,其中9个为新发现变异位点,没有发现错义突变,这种高度保守性说明NEDD4L在维持机体正常生理功能的过程中可能起着至关重要的作用。更多还原

【Abstract】 Objective To identify representative variations of neural precursor cell expressed developmentally down-regulated 4-Like(NEDD4L) gene in hypertensive Kazakh.Methods Ninety-four(47 males and 47 females)hypertensive patients aged 30~60 years were randomly chosen from the Kazakh general population.All exons with their flanking sequences and approximately 500 bp of the upstream region of the promoter of NEDD4L were directly sequenced by an ABI 3130xl genetic analyzer.Results Eleven genetic variations in NEDD4L were identified by sequencing 94 hypertensive individuals,among which there were 3 common SNPs with a minor allele frequency > 10%(271420T>C,271454A>G,and 296921-296923delTTG).296921-296923delTTG was a new genetic common variation in NEDD4L which was not found in the NCBI SNP-database.No missense mutation in NEDD4L was identified,but we identified the following two synonymous mutations:R423(297071G>A in exon14) with a minor allele frequency of 0.91%;and A944(351555C>T in exon 30) with a minor allele frequency of 0.56%.None variation was in tight linkage disequilibrium with an r2<0.5.Conclusion Eleven genetic variations in NEDD4L were identified,among which there were 3 common SNPs and nine were new genetic variations which was not found in the NCBI SNP-database.No missense mutation in NEDD4L was identified.This may be indicative of the relatively high conservation of NEDD4L and the importance of this molecule in regulating salt and water balance and human blood pressure.更多还原