基于二代测序的HMGB1基因SNP发掘及其与溃疡性结肠炎风险关联分析

New SNP digging of HMGB1 gene based on next generation sequencing and association analysis with ulcerative colitis risk

目的探索HMGB1多态性与溃疡性结肠炎(UC)病变风险的相关性。方法利用二代测序技术分别在UC患者和正常对照2个分组的基因混合池中进行转录组测序,将获得的所有序列进行比对分析,从中筛选与UC风险相关的单核苷酸多态性位点;然后利用高分辨率熔解曲线(HRM)验证候选位点。并在含89例(42例UC患者,47例健康对照)中国南方人群中分析各个位点的基因型和等位基因在患病和对照人群中的分布情况。结果共计筛选到候选SNPs位点17个,其中4个位点得到HRM验证。分析发现1个位点(chr13-31127905,T/C)与UC风险密切相关;携带突变基因型(TC+CC)在UC中的比例显著高于对照样本(P=0.018,OR=0.302,95%CI:0.113~0.803)。突变型等位基因C在UC样本中的比例显著高于对照样本(P=0.017,OR=0.357,95%CI:0.157~0.812)。结论携带chr13-31127905位点突变等位基因C的人群罹患UC风险显著高于非携带者。

Objective To investigate the correlation between HMGB1 polymorphism and the ulcerative colitis ( UC) risk. Methods In this study,we used the next generation sequencing technology to carry out transcriptome se- quencing in two groups of DNA pools from UC patients and health controls. All the sequences obtained from transcriptome sequencing were used in screening single nucleotide polymorphism ( SNP) loci that associated with the risk of UC. The candidate SNPs were validated using high resolution fusion curve ( HRM). Aw SNP genotyping experiment was conducted using a case - control study on in a population of 89 patients ( 42 UC patients and 47 healthy controls) from Southern Chi- na. Results A total of 17 candidate SNPs loci were screened out. After HRM analysis,4 sites were validated. The dis- tribution of genotypes and alleles at each locus in the case and control populations were analyzed. One SNP locus ( chr13 - 31127905,T/C) was found to be closely correlated to the risk of UC. Mutation carriers ( TC + CC) proportion in UC was significantly higher than that in the control samples ( P = 0. 018,OR = 0. 302,95% CI: 0. 113 - 0. 803). The mutant allele C proportion in UC samples was significantly higher than that in control samples ( P = 0. 017,OR = 0. 357,95% CI: 0. 157 - 0. 812). Conclusion People with the mutant allele C of chr13 - 31127905 are with higher risk of UC.