溶质相关载体26A3基因多态性与溃疡性结肠炎的相关性

Association of solute-linked carrier family 26 member A3 gene polymorphisms with ulcerative colitis among Chinese patients

目的探讨溶质相关载体26A3（solute—linked carrier family26memberA3，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（rsl7154444、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％眠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-I- 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）. TheCalleleandTC＋CCgenotype 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. 0% 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.