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目的探讨1型糖尿病一级亲属谷氨酸脱羧酶抗体(GADA)、蛋白酪氨酸磷酸酶抗体(IA- 2A)、胰岛素自身抗体(IAA)与HLA-DQ基因型之间的关系。方法横断面、病例对照研究。采用放射配体法检测351例糖耐量正常的1型糖尿病一级亲属与376名正常对照者GADA、IA-2A与IAA。其中156例自身免疫1型糖尿病一级亲属与278名正常对照采用PCR-直接测序法明确HLA-DQ基因型。结果(1)与正常对照比较,1型糖尿病一级亲属DQA1*03、DQB1*0303、*0401等位基因与DQA1*03-DQB1 *0303、DQA1*05-DQB1*0201、DQA1*03-DQB1*0401单体型频率增高(均P<0.05或P<0.01),而DQA1*0601、*0201和DQB1*0301、*0602等位基因与DQA1*0102-DQB1*0602单体型频率减少(均P<0.05或P<0.01)。(2)与1型糖尿病患者比较,1型糖尿病一级亲属DQA1*03等位基因频率减少(45.8%vs 54.5%,P<0.05)。(3)携带DQA1*03-DQB1*0303单体型者,GADA、IA-2A与IAA任一自身抗体阳性率高于不携带此单体型者(23.0%vs 8.6%,P<0.05)。结论携带DQA1*03-DQB1*0303单体型的一级亲属,GADA、IA-2A与IAA任一自身抗体检出率最高。
Objective To investigate the relationship between GADA, IA-2A, IAA and HLA-DQ genotypes in first-degree relatives of type 1 diabetes. Methods Cross-sectional, case-control study. Radioimmunoassay was used to detect GADA, IA-2A and IAA in 351 normal first-degree type 1 diabetic relatives and 376 normal controls. Among 156 cases with autoimmune type 1 diabetes and 278 normal controls, HLA-DQ genotypes were determined by PCR-direct sequencing. RESULTS: Compared with the normal controls, the DQA1 * 03, DQB1 * 0303, and * 0401 alleles of first-degree relatives of type 1 diabetes patients were significantly different from those of DQA1 * 03-DQB1 * 0303, DQA1 * 05-DQB1 * 0201, DQA1 * 03-DQB1 * 0401 haplotype (P <0.05 or P <0.01 respectively), while the frequencies of DQA1 * 0601, * 0201, DQB1 * 0301, * 0602 allele and DQA1 * 0102-DQB1 * 0602 haplotype decreased P <0.05 or P <0.01). (2) Compared with type 1 diabetic patients, the frequency of DQA1 * 03 alleles in type 1 diabetic first-degree relatives decreased (45.8% vs 54.5%, P <0.05). (3) The positive rates of any autoantibody of DQA1 * 03-DQB1 * 0303 haplotype, GADA, IA-2A and IAA were higher than those without this haplotype (23.0% vs 8.6%, P <0.05). CONCLUSION: The first-degree relatives carrying DQA1 * 03-DQB1 * 0303 haplotype have the highest detection rate of any autoantibody of GADA, IA-2A and IAA.