叉头样／翼状螺旋转录因子3基因多态性与克罗恩病易感性和疾病表型的关系  

Relationship between forkhead/winged helix transcription factor 3 gene polymorphisms and susceptibility and phenotype of Crohn＇s disease

作　　者：章达冠 柯乐斌 曹曙光[1] 夏盛隆[1] 卢光荣[1] 林秀清[2] 姜利佳 丁然 蒋益[1] 

机构地区：[1]温州医科大学附属第二医院育英儿童医院消化内科,浙江省325000 [2]温州医科大学附属第一医院消化内科 [3]温州市中心医院消化内科 [4]温州市人民医院消化内科

出　　处：《中华消化杂志》2018年第1期7-13,共7页Chinese Journal of Digestion

基　　金：浙江省自然科学基金（LY14H030012、LY15H030018、LY17H030011）;浙江省卫生厅资助项目（2012KYA132）;温州市科技局资助项目（Y20150157）

摘　　要：目的 探讨浙江籍汉族人群叉头样/翼状螺旋转录因子（Foxp）3基因多态性与CD易感性和疾病表型的关系。 方法 纳入2007年1月至2015年12月确诊的268例CD患者和490名健康对照者，采用多重SNaPshot技术检测其Foxp3的rs3761547、rs2232365、rs2294021、rs3761548 4种单核苷酸多态性（SNP），评价其与英夫利西单克隆抗体疗效的关系，并进行连锁不平衡和单倍型分析。统计学方法采用非条件Logistic回归分析。 结果 31例接受英夫利西单克隆抗体治疗有效与19例无效患者比较，4个SNP的突变等位基因和基因型频率差异均无统计学意义（P均〉0.05）。连锁不平衡分析发现上述4个SNP彼此紧密连锁。男性CD组GCGC单倍型频率为29.20%（40/137），高于男性健康对照组的19.37%（43/222），差异有统计学意义（OR＝1.717，95%CI 1.045～2.820，P＝0.032）；女性CD组ACGA单倍型频率为13.36%（35/262），低于女性健康对照组的19.03%（102/536），差异有统计学意义（OR＝0.656，95%CI 0.433～0.995，P＝0.046）。男性结肠型（L2）ATAC单倍型频率为25.93%（7/27），低于回结肠型（L3）的75.38%（49/65），差异有统计学意义（OR＝0.114，95%CI 0.041～0.320，P〈0.01）；男性结肠型（L2）GCGC单倍型频率为51.85%（14/27），高于回结肠型（L3）的9.23%（6/65），差异有统计学意义（OR＝10.590，95%CI 3.423～32.758，P〈0.01）；男性狭窄型（B2）患者ATAC单倍型频率为73.21%（41/56），高于非狭窄、非穿透型（B1）的47.30%（35/74），差异有统计学意义（OR＝0.328，95%CI 0.156～0.693，P＝0.003）；男性狭窄型（B2）患者GCGC单倍型频率为17.86%（10/56），低于非狭窄、非穿透型（B1）的39.19%（29/74），差异有统计学意义（OR＝2.946，95%CI 1.295～6.784，P＝0.009）；男性穿透型（B3）患者ACGA单倍型频率为71.43%（5/7），高于非狭窄、非穿透型（B1）的12.16%（9/74），差�Objective To investigate the relationship between forkhead/winged helix transcription factor （Foxp） 3 gene polymorphisms and susceptibility and phenotype of Crohn′s disease （CD） in Han nationality in Zhejiang province. Methods From January 2007 to December 2015, 268 diagnosed CD patients and 490 healthy controls were enrolled. The four single nucleotide polymorphism （SNP） of Foxp3 rs3761547, rs2232365, rs2294021 and rs3761548 were examined by a SNaPshot technique, and their relation with the efficacy of infliximab was evaluated. The linkage disequilibrium （LD） and haplotype were also analyzed. Unconditional Logistic regression analysis was performed for statistical analysis. Results There was no significant difference in the four mutant alleles and genotype frequencies between 31 patients with effective infliximab treatment and 19 patients with ineffective treatment （all P〉0.05）. The results of LD analysis indicated that the above four SNP were in a tight linkage. The frequency of haplotype GCGC of male CD group was 29.20% （40/137）, which was higher than that of male healthy control group （19.37%, 43/222）, and the difference was statistically significant （odd ratio （OR）=1.717, 95% confidence interval （CI） 1.045 to 2.820, P=0.032）. The frequency of haplotype ACGA of female CD group was 13.36% （35/262）, which was lower than that of female healthy control group （19.03%, 102/536）, and the difference was statistically significant （OR=0.656, 95%CI 0.433 to 0.995, P=0.046）. The frequency of haplotype ATAC of male colon （L2） type was 25.93% （7/27）, which was lower than that of ileocecal colon （L3） type （75.38%, 49/65）, and the difference was statistically significant （OR=0.114, 95%CI 0.041 to 0.320, P〈0.01）. The frequency of haplotype GCGC of male L2 type was 51.85% （14/27）, which was higher than that of L3 type （9.23%, 6/65）, and the difference was statistically significant （OR=10.590, 95%CI 3.423 to 32.758, P〈0.01）. The fre

关 键 词：CROHN病 基因 多态性 单核苷酸 叉头样/翼状螺旋转录因子3 

分 类 号：R574.62[医药卫生—消化系统]