内蒙古蒙古族和汉族人群白细胞介素12通路相关基因多态性与寻常型银屑病相关性及与HLA-Cw^(*)0602交互作用研究  

Association of interleukin-12 pathway-related gene single nucleotide polymorphisms with psoriasis vulgaris and their interaction with HLA-Cw^(*) 0602 in populations of Mongolian and Han nationalities in Inner Mongolia

作　　者：丁文媛 孙志强[1] 黄艳平[1] 李欣[1] 郭燕 张雪丽 吕新翔[1] 韩建文[1] Ding Wenyuan;Sun Zhiqiang;Huang Yanping;Li Xin;Guo Yan;Zhang Xueli;Lyu Xinxiang;Han Jianwen(Department of Dermatology,The Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,China)

机构地区：[1]内蒙古医科大学附属医院皮肤科,呼和浩特010050

出　　处：《中华皮肤科杂志》2021年第5期414-420,共7页Chinese Journal of Dermatology

基　　金：国家自然科学基金(81660513);内蒙古自治区自然科学基金(2018MS08030);内蒙古自治区科技计划项目(2019GG082);内蒙古医科大学青年创新基金(YKD2018QNCX057)。

摘　　要：目的探讨白细胞介素12(IL-12)通路相关基因多态性与内蒙古蒙古族和汉族寻常型银屑病患者的遗传相关性及与HLA-Cw^(*)0602的交互作用。方法收集2012年12月至2018年3月于内蒙古医科大学附属医院住院的寻常型银屑病患者1409例为病例组,其中汉族1030例,蒙古族379例,健康对照组1483例,其中汉族965例,蒙古族518例。采集受试者外周静脉血5 ml提取DNA,选择位于IL-12B(rs2082412、rs2288831、rs3212227、rs3213094、rs7709212)、IL-23R(rs11209026、rs2201841、rs7530511)、IL-28RA(rs4649203)基因区域的9个单核苷酸多态性(SNP),利用二代测序法进行基因多态性检测,利用序列特异性引物PCR对HLA-Cw^(*)0602进行基因分型。利用PLINK1.07软件进行统计分析,χ^(2)检验比较两组等位基因频率,并计算等位基因的相对危险度估计值比值比(OR),R×C列联表卡方检验进行单倍型分析。结果IL-12B基因rs2082412、rs2288831、rs3212227、rs3213094、rs7709212等位基因频率在汉族病例组显著低于汉族对照组(P<0.005);IL-12B基因rs3213094等位基因频率在蒙古族病例组显著低于蒙古族对照组(P<0.005)。汉族和蒙古族病例组HLA-Cw^(*)0602阳性率均显著高于相应民族对照组(P<0.005)。分层分析显示,汉族HLA-Cw^(*)0602阳性病例组IL-12B基因rs2082412、rs2288831、rs3212227、rs3213094、rs7709212等位基因频率显著低于汉族对照组(P<0.005),而阴性病例组与汉族对照组各等位基因频率差异无统计学意义(P>0.05)。蒙古族HLA-Cw^(*)0602阳性或阴性病例组各等位基因频率与相应对照组差异均无统计学意义(P>0.005)。分析IL-12B基因区域的5个SNP构建单倍型,在汉族、蒙古族病例组和对照组中6个单倍型分析差异均无统计学意义(P>0.005)。基于HLA-Cw^(*)0602分层的IL-12B基因多态性单倍型分析,蒙古族、汉族7个单倍型无论HLA-Cw^(*)0602阳性和阴性病例组及对照组中的频率差异无统计学意义(P>0.005)。HLA-Cw^(*)0Objective To investigate the genetic correlation of interleukin-12(IL-12)pathway-related gene single nucleotide polymorphisms(SNPs)with psoriasis vulgaris and their interaction with HLA-Cw^(*) 0602 in populations of Mongolian and Han nationalities in Inner Mongolia.Methods From December 2012 to March 2018,1409 inpatients with psoriasis vulgaris(1030 of Han nationality and 379 of Mongo-lian nationality)and 1483 healthy controls(965 of Han nationality and 518 of Mongolian nationality)were collected from the Affiliated Hospital of Inner Mongolia Medical University,and served as patient group and control group respectively.Five milliliters of peripheral venous blood samples were collected from these subjects,and DNA was extracted.Nine SNPs located in the coding regions of IL-12 pathway-related genes were selected,including IL-12B(rs2082412,rs2288831,rs3212227,rs3213094,rs7709212),IL-23R(rs11209026,rs2201841,rs7530511)and IL-28RA(rs4649203)genes,and detected by next-generation sequencing.HLA-Cw^(*)0602 was genotyped by polymerase chain reaction with sequence-specific primers(PCR-SSP).Statistical analysis was carried out with PLINK1.07 software,Chi-square test was used to compare allele frequencies between the 2 groups,relative risk estimates of alleles were calculated by using odds ratio(OR),and chi-square test for R×C contingency tables was used for haplotype analysis.Results The allele frequencies of rs2082412,rs2288831,rs3212227,rs3213094 and rs7709212 in the IL-12B gene were significantly lower in the patients with psoriasis vulgaris of Han nationality than in the controls of Han nationality(all P<0.005);the allele frequency of rs3213094 in the IL-12B gene was significantly lower in the patients of Mongolian nationality than in the controls of Mongolian nationality(P<0.005).The prevalence of HLA-Cw^(*) 0602 was significantly lower in the patients with psoriasis vulgaris of Han and Mongolian nationalities than in the controls of corresponding nationalities(both P<0.005).As stratification analysis showed,the allele

关 键 词：银屑病 白细胞介素12 遗传关联研究 多态性 单核苷酸 汉族 蒙古族 HLA抗原 HLA-Cw*0602 交互作用 

分 类 号：R758.63[医药卫生—皮肤病学与性病学]