关键词: 基因芯片, 全基因组关联分析, 单核苷酸多态性, 混合池

Abstract: Objective To discover and identify genetic variants associated with hypertension through using genomewide association study (GWAS). Methods Using a approach which we called SNP-MaP (SNP microarrays and pooling), We conducted a GWAS to explore the association between multigenic polymorphisms and the development of EH in patients with essential hypertension and health controls in Tibetan population from Lhasa. In this study, DNA from patients or controls were pooled and genotyped using an affymetrix genechip array 6.0. After detected the SNP locus, the SNP frequencies were found in patients and controls respectively by sequencing or PCR-RFLP. The relationship between SNPs and EH was analyzed. Results 5 sequence tagged sites met the genomic criteria of P＜9.2×10-8 after Bonferroni correction among whole-genome genetic markers. The differences of genotypes and alleles frequency distributions of the 5 SNP locus was detected by sequencing or PCR-RFLP. The results show that differences of rs17136827 and rs1866525 genotypes and alleles frequency distributions between essential hypertension and healthy controls were not statistically significant, and differences of rs 9865108, rs12541835 and rs 4547758 genotypes and alleles frequency distributions between essential hypertension and healthy controls were statistically significant in population. Conclusions Our results demonstrate that affymetrix human SNP microarrays and pooling provide a very effective platform for genome-wide analysis of SNPs which are susceptible to essential hypertension. The polymorphisms of SNPs(rs 9865108, rs12541835 and rs 4547758 ) are associated with essential hypertension in Tibetan population.

Key words: Gene chip, GWAS, SNP, Pooling