HLA-DQA1基因多态性与儿童Graves’病的相关性研究  

The association between HLA-DQA1 gene polymorphism and Graves' disease of children

作　　者：程昕然[1] 邓蕾丽[1] 熊丰[1] 朱岷[1] 

机构地区：[1]重庆医科大学儿科学院内分泌科,重庆400014

出　　处：《重庆医科大学学报》2003年第4期477-480,共4页Journal of Chongqing Medical University

摘　　要：目的 :分析重庆地区汉族儿童Graves’病 (Graves’disease,GD)与人类白细胞抗原DQA1基因 (HLA -DQA1)多态性的相关性。方法 :用聚合酶链反应 -单链构象多态性 (PCR -SSCP)及DNA测序方法 ,对已经确诊的重庆汉族GD患儿 85例和正常对照组 5 0名儿童的外周血白细胞基因组DNA的HLA -DQA1基因多态性进行分析。结果 :在GD组和对照组中检测到 7种单链构象 ,分别标为abcdefg带型。GD组中d(HLA -DQA1 0 10 2 )、f(HLA -DQA1 0 30 2 / 0 5 0 1)两带型频率 (分别为 4 3.5 % ,VS 8.0 % ;2 7.0 %VS 8.0 % )显著高于正常对照组 (χ2 =18.79,P =0 .0 0 1,RR =8.86 ;χ2 =6 .80 ,P =0 .0 0 9,RR=4 .2 7) ,而b带型 (HLA -DQA1 0 10 1/ 0 30 1)频率 (8.2 %VS 5 2 .0 % )显著低于正常对照组 (χ2 =2 9.4 3,P <0 .0 0 1,RR =0 .0 8)。结论 :HLA -DQA1 0 10 2和HLA -DQA1 0 30 2 / 0 5 0 1可能与GD易感性相关 ,而HLA -DQA1 0 10 1/ 0 30 1可能与GD的保护性相关。提示上述 3基因位点可能分别是重庆地区汉族儿童GD的易感基因和保护基因。Objective:To seek for susceptible and protective gene of GD by analyzing the allele frequency distribution of HLA-DQA1 loci and to evaluate the association of HLA-DQA1 gene polymorphism with GD pathogenesis in Chongqing children of Han race.Methods:Eighty-five children with GD [including 21 boys and 64 girls,mean age (8.84±2.51)] and 50 racially matched healthy controls were recruited for the study.Both groups were of Han race.Genomic DNA was extracted from venous blood samples.Genotypes of HLA-DQA1 were detected by polymerase chain reactions with single strand conformation polymorphism (PCR-SSCP).The results were identified by DNA sequence typing.Frequencies of HLA-DQA1 alleles at eath locus were compared between patients and controls using the χ 2 -test.Results:7 kinds of HLA-DQA1 conformations were found in 85 GD and 50 healthy controls, respectively marked with a b c d e f g.Compared with control group,the frequencies of d and f conformation increased significantly [43.5% VS 8%, χ 2=18.79,P=0.001, relative risk(RR)=8.86;27% VS 8%, χ 2=6.80,P =0.009,RR=4.27],and the frequency of b conformation decreased significantly (8.2% vs 52%, χ 2=29.43,P=0.001, RR=0.08) in GD group.DNA sequence analysis showed that d conformation was HLA-DQAl*0102, f conformation was HLA-DQAl*0302/0501,b conformation was HLA-DQA1*0101/0301.Conclusion:The polymorphism of HLA-DQA1 loci in Chongqing children of Han race are different from that of Caucasian,American Black,Japanese and Hongkong Chinese. It shows that different race and area have different alleles.GD is significantly associated with HLA-DQA1*0102, HLA-DQA1*0302/0501 and HLA-DQA1*0101/0301.It suggests that the HLA-DQA1*0102 and HLA-DQA1*0302/0501 might be the genetic markers for susceptibility, HLA-DQA1*0101/0301 might be the protective genetic markers for GD in Chongqing children of Han race.

关 键 词：Graves’病 人类白细胞抗原 遗传多态性 聚合酶链反应-单链构象多态性 

分 类 号：Q343.15[生物学—遗传学] R729[医药卫生—儿科]