骨保护素基因多态性与贵州省燃煤污染型地方性氟中毒的关联分析  

Association analysis of gene polymorphism of osteoprotegerin with coal-burning endemic fluorosis in Guizhou Province

作　　者：田薇 喻艳琴 赵安宿 张秀秀 王婵娟[1,2] 张婷 单可人[1,2] 何燕 Tian Wei;Yu Yanqin;Zhao Ansu;Zhang Xiuxiu;Wang Chanjuan;Zhang Ting;Shan Keren;He Yan(Key Laboratory of Endemic and Ethnic Diseases,Ministry of Education,Guizhou Medical University,Guiyang 550004,China;Key Laboratory of Molecular Biology of Guizhou Province,Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]贵州医科大学地方病与少数民族疾病教育部重点实验室,贵阳550004 [2]贵州医科大学贵州省医学分子生物学重点实验室,贵阳550004

出　　处：《中华地方病学杂志》2020年第9期641-646,共6页Chinese Journal of Endemiology

基　　金：贵州省科技支撑计划项目(黔科合支撑(2019)2807)。

摘　　要：目的探讨骨保护素(OPG)基因多态性与贵州省燃煤污染型地方性氟中毒(简称燃煤型地氟病)的关系。方法2018、2019年,采用病例对照研究方法,在贵州省典型燃煤型地氟病病区毕节市选取燃煤型地氟病患者260例作为病例组,根据《地方性氟骨症诊断标准》(WS 192-2008)将病例组分为重症组和轻症组,每组130例;同时,在贵州省非燃煤型地氟病病区长顺县选取无氟斑牙及氟骨症症状者130例作为对照组。提取研究对象全血基因组DNA,采用TaqMan-MGB探针实时荧光定量PCR法对所有样本OPG基因rs2460985、rs2073618、rs6469804、rs69938134个单核苷酸多态性(SNP)位点进行基因分型和遗传模式分析,比较其等位基因、基因型及所构建的单倍型在对照、轻症、重症组中频率分布的差异。结果经Hardy-Weinberg平衡检验,4个SNP位点基因型频率在对照、轻症、重症组中均达到遗传平衡(P均>0.05)。OPG基因rs6469804位点基因型频率组间比较差异有统计学意义(χ2=10.615,P<0.05),且该位点基因型频率对照组与重症组比较差异有统计学意义(χ2=6.784,P<0.05)。遗传模式分析结果显示,rs6469804位点对照组与重症组比较最优遗传模式为超显性遗传模式,在该模式下基因型AA+GG和AG频率分布差异有统计学意义[比值比(OR)=1.94,95%置信区间(CI):1.16~3.23,P<0.05],基因型AG是燃煤型地氟病发生的危险因素;rs2073618位点对照组与轻症组比较最优遗传模式为隐性遗传模式,在该模式下基因型GG+GC和CC频率分布差异有统计学意义(OR=3.17,95%CI:1.08~9.30,P<0.05),基因型CC是燃煤型地氟病发生的危险因素。对照组与轻症组比较,单倍型C-C-G-T、T-G-A-C是燃煤型地氟病发生的危险因素(调整OR=2.41、1.98,95%CI:1.29~4.50、1.22~3.23,P均<0.05);对照组与重症组比较,单倍型T-G-A-C是燃煤型地氟病发生的危险因素(调整OR=1.87,95%CI:1.14~3.07,P<0.05)。结论OPG基因rs6469804位点基因型AG和rs207Objective To investigate the relationship between gene polymorphism of osteoprotegerin(OPG)and coal-burning endemic fluorosis in Guizhou Province.Methods In 2018 and 2019,a case-control study was conducted in Bijie City,a typical coal-burning endemic fluorosis area in Guizhou Province,and 260 cases of coal-burning endemic fluorosis patients were selected as case group.According to the"Diagnostic Criteria for Endemic Skeletal Fluorosis"(WS 192-2008),the case group was divided into severe group(130 cases)and mild group(130 cases).At the same time,130 cases without dental fluorosis and skeletal fluorosis symptoms were chosen as control group in Changshun County,a non-coal-burning endemic fluorosis area in Guizhou Province.Whole blood genomic DNA was extracted,and real-time fluorescence quantitative PCR with TaqMan-MGB probe was utilized to type the OPG gene rs2460985,rs2073618,rs6469804 and rs6993813 four single nucleotide polymorphism(SNP)loci of all samples,and genetic model analysis was performed to compare the frequency distribution of its alleles,genotypes and constructed haplotypes in control,mild and severe groups.Results By Hardy-Weinberg equilibrium test,the genotype frequencies of the four SNP loci all reached genetic balance in control,mild and severe groups(P>0.05).There was a statistically significant difference in the genotype frequency of OPG gene rs6469804 locus among the three groups(χ2=10.615,P<0.05),and the difference in the genotype frequency of this locus between the control group and the severe group was statistically significant(χ2=6.784,P<0.05).The results of genetic model analysis showed that in comparison between the control group and the severe group,the optimal genetic model of rs6469804 locus was the overdominant genetic model,the frequency distribution of genotypes AA+GG and AG in the control group and the severe group was statistically significant[odds ratio(OR)=1.94,95%confidence interval(CI):1.16-3.23,P<0.05],genotype AG was a risk factor for coal-burning endemic fluorosis.In compa

关 键 词：骨保护素 氟中毒 基因多态性 单倍型 

分 类 号：R599.1[医药卫生—内科学]