Identification of common variants within KCNK17 in Chinese Han population / 华中科技大学学报（医学）（英德文版）

ABSTRACT

KCNK17 is a member of the acid-sensitive subfamily of tandem pore K(+) channels, which are open at all membrane potentials an red contribute to cellular resting membrane potential. Recent genome-wide study (GWA) has shown that variants within KCNK17 confer genetic susceptibility for increasing ischemic stroke. In an effort to discover additional polymorphism(s), we scrutinized the genetic polymorphisms in the KCNK17. By direct DNA sequencing in 32 individuals, we identified nine sequence variants within the 16 kb of whole KCNK17 gene one in exon1, one in intron and seven in the promoter region. Haplotypes, their frequencies and linkage disequilibrium coefficients (D'), among polymorphisms were estimated. All the polymorphisms in the 5'-flanking region (SNP2-SNP7) being in complete (or nearly complete) association with each other in the promoter region maybe produce synergistic effect to regulate the expression of KCNK17 gene and then have an influence on the pathogenesis of cerebrovascular diseases. The common haplotypes were observed comprising 88.9% of the total haplotypes in the same block. Bioinformatic analysis predicted several potential transcriptional factors binding sites by SNP -95, -134, -596 and -846. However, these binding sites need to be experimentally verified. The information concerning genetic polymorphisms of KCNK17 gene might provide valuable information for future genetic studies of diseases.