白细胞免疫球蛋白活化受体3与炎症性肠病的关系研究  

Association between leukocyte immunoglobulin like receptor A3 and the susceptibility to inflammatory bowel disease

作　　者：张小敏[1] 周峰[1] 兰秀彩[1] 黄梅芳[1] 

机构地区：[1]武汉大学中南医院消化内科,湖北武汉430071

出　　处：《临床消化病杂志》2017年第2期91-97,共7页Chinese Journal of Clinical Gastroenterology

摘　　要：[目的]探讨中国汉族人群中白细胞免疫球蛋白活化受体A3(LILRA3)基因多态性与炎症性肠病(IBD)发病的关系。[方法]收集378例确诊IBD患者[溃疡性结肠炎(UC)组193例,克罗恩病(CD)组185例]和509例健康者(正常对照组),通过连接酶检测反应-聚合酶链反应(LDR-PCR)技术分析LILRA3基因第1内含子第161位碱基(G→C突变)多态性。对所有入选者使用实时定量PCR(qRT-PCR)方法检测外周血、肠黏膜中LILRA3mRNA表达情况,使用Western blotting方法检测肠黏膜中LILRA3蛋白表达。[结果]所有纳入样本中均未发现LILRA3基因第1内含子第161位的纯合子突变(CC)。CD组患者该位点突变基因型频率与等位基因频率均明显低于正常对照组,差异具有统计学意义(P值分别为0.017,0.021),且突变基因型GC及突变等位基因C是CD发病的保护因素(OR=0.489,95%CI:0.269~0.890;OR=0.509,95%CI:0.284~0.914)。基因型与临床表型相关性分析提示:突变基因型GC与CD17-40岁发病及CD炎症型疾病行为相关(P值分别为0.039,0.049),且均是保护性因素(OR=0.490,95%CI:0.245~0.977;OR=0.473,95%CI:0.221~0.953)。UC组与正常对照组相比该位点基因型频率与等位基因频率分布无差异(P>0.05)。qRT-PCR结果提示:1 CD组、UC组患者外周血LILRA3mRNA表达量均明显高于正常对照组[(14.25±2.29)、(15.71±2.74)∶(7.54±1.26)],差异具有统计学意义(P值分别为0.035,0.025);2突变个体(GC)LILRA3表达量明显高于野生型个体(GG)[(27.58±3.70)∶(10±1.39)],差异具有统计学意义(P<0.001);3 CD、UC组患者肠黏膜LILRA3mRNA表达量也明显高于正常对照组[(14.31±0.88)、(13.87±0.98)∶(2.29±2.88)],差异具有统计学意义(P<0.001)。与对照组相比,CD组、UC组肠黏膜LILRA3蛋白表达量均明显升高[(0.55±0.82)、(0.59±0.13)∶(0.27±0.09)],差异具有统计学意义(P<0.001)。[结论]LILRA3基因第1内含子第161位基因多态性与IBD发病相关,且突变影响其mRNA表达。IBD患者外周血�[Objective]To investigate the association between LILRA3 gene polymorphism and inflammatory bowel disease（IBD） development in Chinese Han population.[Methods]The total of 378 IBD patients（193 ulcerative colitis[UC],185 Crohn＆#39;s disease[CD]）and 509 healthy controls were recruited.Genotyping for LILRA3 161 base of intron 1 polymorphism（G→C mutation）was analyzed by PCR-LDR assay.qRT-PCR was employed to examine the relative mRNA levels of LILRA3 both in peripheral blood and mucosa of patients and healthy controls.The protein levels of LILRA3 in mucosa were examined by western blotting.[Results]No homozygotic mutant genotype（CC）was detected among the involved subjects.CD patients showed dramatically lower frequencies of mutant genotype GC and allele C compared with those of healthy controls（7.6% vs 14.3%,P=0.017;3.8% vs 7.2%,P=0.021）.However,no significant difference was detected between UC and healthy controls for genotype frequency or allele frequency（P〉0.05）.Genotype-phenotype analysis showed that CD patients possessing mutant genotype（GC）were less likely to develop CD between 17 to 40 years old（P=0.039,OR=0.49,95%CI：0.25-0.98）,and less likely to suffer intestinal complications including stenosis and punching （P =0.049,OR =0.46,95 % CI：0.23-0.95）.Additionally,CD and UC patients showed significantly higher LILRA3 mRNA levels compared to healthy controls both in perpheral blood（[14.25＆#177;2.29],[15.71＆#177;2.74]vs[7.54＆#177;1.26],P=0.035,0.025）and in mucosa（[14.31＆#177;0.88],[13.87＆#177;0.98]vs[2.29＆#177;2.88],P〈0.001）.Interestingly,we found that the subjects possessing mutant genotype GC showed significantly higher LILRA3 mRNA levels than those with genotype GG（[27.58＆#177;3.70]vs[10＆#177; 1.39],P〈0.001）.Higher LILRA3 protein levels were also found in CD and UC patients than that of healthy controls（[0.55＆#177;0.82],[0.59＆#177;0.13]vs[0.27＆#177;0.09],P〈0.001）.[Conclusion]LILRA3 polymorphism of 161 base of intron 1 of LILRA3

关 键 词：炎症性肠病 白细胞免疫球蛋白活化受体3 基因多态性 遗传易感性 

分 类 号：R574.62[医药卫生—消化系统]