1型糖尿病患者人类白细胞抗原Ⅰ类基因与胰岛功能及胰岛自身抗体的关系  

Associations of human leukocyte antigen Ⅰ gene with islet function and islet autoantibodies in type 1 diabetes mellitus

作　　者：施云[1] 沈捷[2] 顾愹[1] 蔡赟[1] 杨帆[1] 张青青[1] 毛佳[1] 陈恒[1] 徐宽枫[1] 许馨予[1] 张梅[1] 石星[3] 朱妍[4] 卜瑞芳[5] 李伟[6] 成兴波[7] 成金罗[8] 俞伟男[9] 陆卫平[10] 吴晨光 杨涛[1] 

机构地区：[1]南京医科大学第一附属医院内分泌科,210029 [2]南京医科大学第一附属医院HLA实验室,210029 [3]南京市儿童医院内分泌科 [4]江苏省苏北人民医院内分泌科 [5]无锡市人民医院内分泌科 [6]徐州医学院附属医院内分泌科 [7]苏州大学第一附属医院内分泌科 [8]常州市第二人民医院内分泌科 [9]淮安市第二人民医院内分泌科 [10]淮安市第一人民医院内分泌科 [11]镇江市第一医院内分泌科

出　　处：《中华糖尿病杂志》2013年第7期392-397,共6页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：国家自然科学基金项目（30971405、81270897）;＂973＂计划前期研究专项基金项目（2010CB535008）

摘　　要：目的 探讨1型糖尿病（T1DM）患者胰岛功能、胰岛自身抗体[谷氨酸脱羧酶抗体（GADA）、蛋白酪氨酸磷酸酶抗体（IA-2A）、胰岛素自身抗体（IAA）和阳离子外流锌转运体蛋白抗体（ZnT8A）]与人类白细胞抗原（HLA）Ⅰ类等位基因的关系.方法 选取2008年6月至2012年10月在南京医科大学第一附属医院及其开放课题26家医院（共同组成江苏省T1DM合作组）内分泌科就诊的T1DM患者330例.采用聚合酶链反应-寡核苷酸探针序列特异性引物（PCR-SSO）技术进行T1DM患者HLAⅠ类基因（A、B基因）分型,放射免疫配体法检测胰岛自身抗体（GADA、ZnT8A、IA-2A、IAA）.选择同地区、遗传背景相近的中华骨髓库无关供者HLA分型资料20 248份作为研究对照.通过Arlequin软件进行HL4Ⅰ类等位基因频率及单倍型频率分析.定量资料的组间比较采用独立样本的t检验.结果 与对照组相比,T1DM组HLA-A＊24、B＊08、B＊41、B＊54、B＊58频率明显升高（OR=1.250、2.062、6.927、2.472、1.608,均P＜0.05）；A＊01、B＊07、B＊27、B＊52、B＊57频率显著下降（OR =0.481、0.464、0.372、0.160、0.315,均P＜0.05）；HLA-A＊24-B＊ 54单倍型频率明显升高（OR=4.128,P＜0.05）.携带A＊02基因位点的T1DM患者其空腹C肽水平高于不携带A ＊02的患者[（356±249）比（250±199） pmol/L,t=-3.004,P＜O.05].未发现HLAⅠ类基因与胰岛自身抗体存在统计学关联.结论 江苏地区汉族T1DM患者中,HLAⅠ类等位基因不仅可影响T1DM的发病风险,而且可能影响发病后胰岛功能的衰竭速度.Objective To explore the relationships of human leukocyte antigen （HLA） I gene frequency with islet function and the four islet autoantibodies （glutamic acid decarboxylase antibody （GADA）, zinc transporter 8 antibody （ZnT8A）, protein tyrosine phosphatase-2 antibody （IA-2A） and insulin autoantibody （IAA）） in Chinese patients with type 1 diabetes mellitus （T1DM） in Jiangsu Province. Methods A total of 330 patients with T1DM treated in 26 centers in Jiangsu Province from June 2008 to October 2012 were included in this data set. The H/A-I gene was genotyped by the polymerase chain reaction-sequence oligonucleotide probe system method （PCR-SSO）, and the four islet antibodies were detected by radioligand assay. HLA-typing control data were drawn from 20 248 individuals in the Chinese Marrow Donor Program with similar genetic backgrounds. The frequencies of HLA alleles and haplotypes were analysed by Arlequin software. The independent sample t test was used in comparison of quantitative data. Results Compared with those in controls, the frequencies of HLA-A ＊ 24, B ＊ 08, B ＊ 41, B ＊ 54, B ＊ 58 were significantly higher （ OR = 1. 250, 2. 062, 6. 927, 2. 472, 1. 608, all P 〈 0. 05） and that of A ＊ 01, B ＊ 07, B ＊ 27, B ＊ 52, B ＊ 57 were significantly lower （OR = 0. 481, 0.464, 0. 372, 0. 160, 0. 315, all P 〈 0. 05） in patients with T1DM; the frequency of HLA-A ＊ 24-B ＊ 54 haplotype was significantly higher （ OR = 4. 128, P 〈 0. 05 ） in patients with T1DM. The T1 DM individuals with the A ＊ 02 gene locus had a higher fasting C peptide level than those without A ＊ 02（ （356 ±249 ） vs （250 ± 199 ） pmol/L, t = - 3. 004, P 〈 0. 05 ）. No relationships between HLA I gene and four autoantibodies were found in those patients. Conclusions Among T1DM patients in the Jiangsu Han ethnic group, the HLA I loci may affect the their susceptibility to T1DM and the destruction rate of pancreatic β cell.

关 键 词：糖尿病 1型 人白细胞抗原 C肽 胰岛自身抗体 

分 类 号：R587.1[医药卫生—内分泌]