细胞因子基因多态性与肺结核并发糖尿病易感性的相关性研究  

Association of cytokine genetic polymorphisms with susceptibility to diabetic pulmonary tuberculosis

作　　者：董斯佳 袁立[1] 陈诚[2] 蒋伟利[1] 赵琦[1] DONG Si-jia;YUAN Li;CHEN Cheng;JIANG Wei-li;ZHAO Qi(Department of Epidemiology,School of Public Health,Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学公共卫生学院流行病学教研室公共卫生安全教育部重点实验室,上海200032 [2]江苏省疾病预防控制中心慢性传染病防治所,上海200032

出　　处：《中国防痨杂志》2018年第10期1051-1059,共9页Chinese Journal of Antituberculosis

基　　金：国家自然科学基金（81202256）

摘　　要：目的探索细胞因子γ-干扰素（IFN-γ）＋874A／T位点、白细胞介素（IL）-10-1082G／A位点和-592A／C位点基因多态性与肺结核并发糖尿病（pulmonary tuberculosisanddiabetic mellitus，PTB-DM）易感性的关系，以及遗传危险因素在PTB-DM发病机制中的作用，为PTB-DM高危人群基因多态性筛查提供理论依据。方法采用病例对照研究方法，纳入江苏省2013年4月1日至2014年3月31日3个市（县）142例PTB-DM患者（PTB-DM组），同期选取诊断为结核病的患者147例（TB组）和糖尿病患者141例（DM组）作为对照。通过结构式问卷调查获取研究对象社会人口学信息，采集患者血样并提取DNA，采用聚合酶链式反应并限制性片段长度多态性（polymerase chain reaction-restriction fragment length plymorphism，PCR-RFIF）方法检测IFIFN＋874A／T位点、IL-10-1082G／A位点和-592A／C位点基因多态性。采用EpEPiData和SPSS16．O统计软件录入与分析数据，运用单因素方差分析和多因素logistic回归分析I附7＋874A／T位点、IL-10-1082G／A位点和-592A／C位点基因多态性与PT昏DM易感性的相关性。结果IFN-γ十874A／T、IL-10一592A／C、IL-10-1082G／A位点经PCR扩增和基因多态性位点分型鉴定，分别获得等位基因A和T、A和C、G和A，以及基因型AA、AT、TT；AA、AC、CC；GA、AA。基因多态性检测结果显示，仅PT昏DM组IL-10-1082G／A位点A等位基因频率（92．61％，263／284）高于DM组（87．59％，247／282）（χ^2=3．995，P=O．046）、AA基因型频率（85．21％，121／142）高于DM组（75．18％，106／141）[校正OR（αOR）-1．970；95％CI：1．066-3．643；P=0．030]。IL-10-592和-1082两位点间存在连锁不平衡（D=0．959，-0．181，P〈O．001），PTB-DM患者的IL-10 C-A单倍型频率（25．90％）明显高于DM组患者（17．60％）（OR=1．590，95％CI=1．056-2．396，P=0．026）。结论IL-10-1082位点的从基因型可能与PT�Objective This study aims to reveal the associations among IFN-γ ＋874 A/T, IL-10 --592 A/C, --1082 G/A SNPs and risk of diabetic pulmonary tuberculosis, and consequently provide further evidence for research on pathogenesis of diabetic pulmonary tuberculosis （PTB-DM） and the screening for diabetic pulmonary tuberculosis patients. Methods A case-control study based on the screening of DM in PTB patients （142 cases） was carried out in 3 counties in Jiangsu Province from 1 April, 2013 to 31 March, 2014. Cases in this study were all diagnosed diabetic pulmonary tuberculosis patients, whereas control groups were PTB patients （147 cases） and DM patients （141 cases） matching with gender and age. Social demographic information was collected by a questionnaireand DNA was extracted from the blood sample collected. The polymorphisms of IFN--＇ -5874 A/T, IL-10 --592 A/C and --1082 G/A were detected by PCR-RFLF methods and followed by direct sequencing. Statistical analyses were conducted using the EpiData and SPSS software version 16.0. Pearson chi-square and logistic regression were used to estimate the associations among IFN-＇I ＋874 A/T, IL-10 -- 592 A/C, -- 1082 G/A SNPs and risk of diabetic pulmonary tuberculosis. Results In the study on IL-10 --1082 G/A, statistical differences were discovered between PTB-DM patients and DM controls （A allele, 92.61- （263/284） versus 87.59% （247/282）（;g2 =3. 995, P=0. 046） ; AA genotype, 85.21G （121/142） versus 75.18G （106/141）. The AA genotype of IL-10 had a 1. 970 fold increased risk for diabetic pulmonary tuberculosis individuals （OR= 1. 970, 95% CI= 1. 066--3. 643, respec- tively）. Linkage disequilibrium was found between IL-10 -- 592 and IL-10 -- 1082 （D＇ = 0. 959, r2 ----- 0. 181, P- 0. 001） and statistical significance was also found in ILl0 --592C/--1082A haplotype between diabetic pulmonary tuberculosis patients and DM controls （25.90-/＇00 versus 17.60%, P= 0. 026）; IL-10 --592C/--1082A haplotype had a 1. 590 fold i

关 键 词：结核 肺 糖尿病 共病现象 细胞因子类 扩增片段长度多态性分析 疾病易感性 遗传相关性研究 

分 类 号：R699.2[医药卫生—泌尿科学]