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目的探讨急性起病1型糖尿病(T1DM)患者谷氨酸脱羧酶抗体(GADA)、蛋白酪氨酸磷酸酶抗体(TA-2A)、胰岛素自身抗体(IAA)与人类白细胞抗原(HLA-DQ)基因型之间的关系。方法采用横断面、病例对照研究方法,495例 T1DM 患者与376例正常对照用放射配体法检测GADA 和 IA-2A,其中使用胰岛素在2周以内的71例患者与300例正常对照检测 IAA。187例抗体阳性、151例抗体阴性 T1DM 患者与278例正常对照采用 PCR 直接测序法确定 HLA-DQ 基因型。结果(1)与正常对照比较,T1DM 患者(n=187)DQA1*03-DQB1*0303、DQA1*05-DQB1*0201与 DQA1*03-DQB1*0401单体型频率增高(分别为32.6% vs 21.9%,14.1% vs 3.5%与10.2% vs 2.9%,均P<0.01),DQA1*0102-DQB1*0602单体型频率降低(1.7% vs 5.3%,P<0.05),而 DQA1*03-DQB1*0302频率差异无统计学意义(4.7% vs 3.8%,P>0.05)。(2)在338例 T1DM 患者中,携带DQA1*05-DQB1*0201与 DQA1*03-DQB1*0401单体型患者,GADA 阳性率高于不携带此单体型者(分别为55.8% vs 41.0%与65.5% vs 40.3%,P<0.05或 P<0.01);携带 DQA1*03-DQB1*0303单体型患者 IA-2A 阳性率高于不携带此单体型者(27.0% vs 7.9%,P<0.01);携带 DQA1*03-DQB1*0302单体型患者 GADA 与 IA-2A 阳性率分别与不携带此单体型者比较,差异均无统计学意义(48.5% vs 43.9%与24.2% vs 15.4%,P>0.05);而携带保护性 DQA1*0102-DQB1*0602单体型患者 GADA 阳性率低于不携带此单体型者(16.7% vs 45.9%,P<0.05)。携带易感单体型者 IAA 检出率与不携带者比较,差异均无统计学意义(P>0.05)。结论 1型糖尿病患者 GADA 与 DQA1*05-DQB1*0201、DQA1*03-DQB1*0401单体型相关,IA-2A 与 DQA1*03-DQB1*0303单体型相关。
Objective To investigate the effects of GADA, TA-2A, IAA and HLA-DQ on patients with type 1 diabetes mellitus (T1DM) Relationship between genotypes. Methods GADA and IA-2A were detected by radioligand assay in 495 patients with T1DM and 376 normal controls using cross-sectional and case-control study. 71 patients with insulin in less than 2 weeks and 300 normal controls were used to detect IAA. 187 cases of antibody positive, 151 cases of antibody negative T1DM patients and 278 normal controls using PCR direct sequencing to determine the HLA-DQ genotype. RESULTS: (1) The frequencies of haplotypes in DQA1 * 03-DQB1 * 0303, DQA1 * 05-DQB1 * 0201 and DQA1 * 03-DQB1 * 0401 were significantly higher in T1DM patients (n = 187 vs 32.6% vs The frequency of DQA1 * 0102-DQB1 * 0602 haplotype decreased (1.7% vs 5.3%, P <0.05), but DQA1 * 03- DQB1 * 0302 frequency difference was not statistically significant (4.7% vs 3.8%, P> 0.05). (2) In 338 patients with T1DM, the positive rate of GADA was higher in patients with DQA1 * 05-DQB1 * 0201 and DQA1 * 03-DQB1 * 0401 haplotype than those without this haplotype (55.8% vs 41.0 The positive rates of IA-2A in patients with DQA1 * 03-DQB1 * 0303 haplotype were higher than those without this haplotype (27.0% vs 7.9%, P <0.05 or P <0.01) P <0.01). The positive rates of GADA and IA-2A in patients with DQA1 * 03-DQB1 * 0302 haplotype were not significantly different from those without this haplotype (48.5% vs 43.9% vs 24.2% vs 15.4%, P> 0.05). However, the positive rate of GADA in patients with protective haplotype DQA1 * 0102-DQB1 * 0602 was lower than those without this haplotype (16.7% vs 45.9%, P <0.05). There was no significant difference in the detection rate of IAA between those with and without carriers (P> 0.05). Conclusions GADA is associated with haplotypes DQA1 * 05-DQB1 * 0201 and DQA1 * 03-DQB1 * 0401 in patients with type 1 diabetes mellitus, and IA-2A is associated with haplotype DQA1 * 03-DQB1 * 0303.