溶质相关载体26A3基因多态性与溃疡性结肠炎的相关性

摘要

目的 探讨溶质相关载体26A3(solute-linked carrier family 26 member A3,SLC26A3)基因单核苷酸多态性(single nucleotide polymorphism,SNP)及单倍型与溃疡性结肠炎(ulcerative colitis,UC)的相关性.方法 收集416例UC患者和584名正常对照者,应用多重SNaPshot技术检测SLC26A3(rs17154444、rs7810937、rs7785539、rs2108225和rs6951457)5个SNP位点的等位基因及基因型,并进行连锁不平衡和单倍型分析.结果 UC组中(rs2108225)等位基因(G)和基因型(AG+GG)的频率均高于对照组(65.14％vs.58.65％,P=0.030;87.02％ vs.81.85％,P=0.012).与轻中度UC患者相比,重度UC患者中(rs17154444)等位基因(C)和基因型(TC+ CC)的频率及(rs7785539)等位基因(C)和基因型(GC+CC)的频率均显著增高(rs17154444:14.00％ vs.6.01％,28.00％ vs.11.48％,P均＜0.01;rs7785539:8.00％ vs.7.38％,P=0.011;16.00％ vs.13.93％,P=0.017). rs17154444,rs7810937,rs7785539和rs2108225)4个SNP位点彼此连锁.与对照组相比,UC组中单倍型(T-A-G-G)的频率增高(62.60％ vs.58.20％,P=0.017);而单倍型(T-G-G-A)的频率降低(27.40％vs.31.60％,P=0.041).结论 SLC26A3 (rs2108225)基因变异可能增加UC发病风险,rs17154444和rs7785539基因多态性与UC严重程度相关.携带rs17154444,rs7810937,rs7785539和rs2108225构建的单倍型(T-A-G-G)可能增加UC发病风险,而单倍型(T-G-G-A)可能降低UC发病风险.%Objective To assess the association of single nucleotide polymorphisms (SNPs) and haplotypes of solute-linked carrier family 26 member A3 (SLC26A3)gene with ulcerative colitis (UC) among Chinese patients.Methods For 416 UC patients and 584 controls,5 SNPs of the SLC26A3 gene (rs17154444,rs7810937,rs7785539,rs2108225 and rs6951457) were determined with a SNaPshot method.Linkage disequilibrium (LD) and haplotype were analyzed for all subjects.Results The G allele and AG+ GG genotype of rs2108225 were more prevalent in UC patients compared with the controls (65.14％ vs.58.65％,P=0.030;87.02％ vs.81.85％,P=0.012,respectively).The C allele and TC+CC genotype of rs17154444 were more prevalent in patients with severe UC than in other patients (14.00％ vs.6.01 ％,P＜0.01;28.00％ vs.11.48％,all P＜0.01).Similar conclusion may also be drawn for C allele and GC+ CCgenotype of rs7785539 (8.00％ vs.7.38％,P=0.011;16.00％ vs.13.93％,P=0.017,respectively).The SNPs rs17154444,rs7810937,rs7785539 and rs2108225 were found to be in strong LD.Compared with the controls,the T-A-G-G haplotype was more prevalent in UC patients (62.60％ vs.58.20％,P=0.017),whereas the T-G-G-A haplotype was less common in UC patients (27.40％ vs.31.60％,P=0.041).Conclusion Variations of the SLC26A3 rs2108225 may enhance the risk of UC.The rs17154444 and rs7785539 polymorphisms of the SLC26A3 gene are correlated with the severity of UC.The T-A-G-G haplotype formed by rs17154444,rs781093,rs7785539 and rs2108225 of the SLC26A3 gene may increase the risk for UC,whereas the T-G-G-A haplotype may decrease this risk.