1型糖尿病患者自身抗体与HLA-A等位基因的关系

Relationship between islet autoantibodies and HLA-A gene in type 1 diabetes mellitus

目的:探讨急性起病的1型糖尿病(T1DM)患者血清谷氨酸脱羧酶抗体(GADA)、胰岛细胞抗体(ICA)、胰岛素自身抗体(IAA)与HLA-A等位基因之间的关系。方法:采用酶联免疫吸附法(ELISA)定性检测104例江苏地区汉族T1DM患者与110例正常对照的GADA、ICA和IAA。从外周血中提取细胞基因组DNA,运用聚合酶链反应-寡核苷酸探针序列特异性引物(PCR-SSO)技术,检测T1DM患者和正常对照的HLA-A基因频率。应用SPSS11.0软件进行T1DM发病年龄及自身抗体与HLA-A基因频率的相关性分析。结果:T1DM组与正常对照组相比,A*03、A*24频率明显升高,A*01、A*11、A*31频率明显下降。起病年龄20岁以下的急性起病T1DM患者与20岁以上患者比较,携带HLA-A*24基因型频率增高,而HLA-A*31等位基因频率减少。携带HLA-A*03等位基因的急性起病T1DM患者GADA、ICA阳性率高于不携带A*03者;携带HLA-A*24等位基因的急性起病T1DM者ICA阳性率高于不携带A*24者。结论:本研究发现在江苏地区急性起病的T1DM患者中,A*03、A*24是易感基因,而A*01、A*11、A*31是保护性基因,A*31可能延缓1型糖尿病的发病;A*31与发病年龄正相关,ICA、A*24与发病年龄负相关;A*03、A*24与GADA正相关,A*24与ICA正相关。

Objective：To explore the relationship between islet autoantibodies of glutamic acid decarboxylase antibody （GADA）,islet cell antibody（ICA） and insulin autoantibody（IAA） and HLA-A gene in patients with type 1 diabetes mellitus（T1DM） in Jiangsu province.Methods：One hundred and four patients with type 1 diabetes in Chinese Han of Jiangsu area and 110 healthy controls were recruited and measured for GADA,IAA,ICA by ELISA.HLA-A typing was performed by polymerase chain reaction-sequence specific oligonucleotide primer （PCR-SSO） technology after extracted genomic DNA from peripheral blood cells.The HLA-A alleles frequencies were studied by Arlequin software.Then an analysis was made on the correlation between islet autoantibodies of GADA,IAA,ICA and HLA-A alleles in type 1 diabetes mellitus by SPSS 11.0.Results：The positivity frequencies of GADA,ICA and IAA in 104 type 1 diabetes patients were 64.4%,39.4% and 37.5%,respectively.The frenquencies of HLA-A＊03 and HLA-A＊24 alleles in the patients were significantly higher than that in healthy control group.The frenquencies of HLA-A＊01,HLA-A＊11,HLA-A＊31 alleles in the patients of acute autoimmune diabetes were significantly lower than those in the healthy control group.In patients,whose onset age 20 years,the frequency of A＊24 alleles was higher than that in the patients with onset age ≥20 years,but the frequency of A＊31 alleles in acute-onset autoimmune diabetes with onset age 20 years was lower than that in the patients with onset age ≥20 years.The frequencies of GADA,ICA positivity were higher in those patients with A＊03 alleles than those in patients lacking it;the frequency of ICA positivity was higher in those patients with A＊24 alleles than those in patients lacking it.Conclusion：Our findings show that HLA-A＊03 and A＊24 are susceptibility to acute-onset autoimmune diabetes,whereas HLA-A＊01,A＊11 and A＊31 are protective in Jiangsu province.A＊31 may delay the onset of acute-onset autoimmune diabetes,A＊31 is correlated positively with age at onset;while ICA,A＊24 are negatively correlated with age at onset.A＊3,A＊24 are positively correlated with GADA,and A＊24 is positively correlated with ICA.