与北印度儿童1型糖尿病相关的人类白细胞抗原单倍型

HLA haplotypes associated with type 1 diabetes mellitus in North Indian children.

作者信息

Kanga Uma, Vaidyanathan Balu, Jaini Ritika, Menon Puthezath S N, Mehra Narinder K

机构信息

Department of Transplant Immunology, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Hum Immunol. 2004 Jan;65(1):47-53. doi: 10.1016/j.humimm.2003.10.013.

DOI:10.1016/j.humimm.2003.10.013

PMID:14700595

Abstract

Human leukocyte antigen (HLA) encoded susceptibility to develop type 1 diabetes mellitus (T1DM) has been investigated in children from North India. The results revealed significantly increased prevalence of HLA-A26, -B8, and -B50 among patients and strong positive association of the disease with DRB10301 (82.1% vs 13.9%, chi2=71.3, odds ratio [OR]=28.3) and a negative association with DRB102 (chi2=12.2, PF=38.5). HLA-DQB10201 occurred in 96.4% of the patients, whereas the heterodimer DQA10501-DQB10201 was present in 82.1% of patients (60.7% in single dose and 21.4% in double dose) and revealed significant deviation from the healthy controls (chi2=74.1, pc=6.0E-10). In addition to DRB103, positive association was also observed with DRB109 (14.3% vs 1.3%, chi2=13.4) and DRB104 (39.3% vs 15.6%, chi2=8.39). No HLA association was observed in relation to residual pancreatic beta-cell function or associated thyroid autoimmunity. Family analysis revealed involvement of multiple DR3+ve haplotypes with T1DM in North Indian children with A26-B8-DRB103 (25% vs 3.5%, chi2=16.9, p=3.96E-05) and Ax-B50-DRB103 (25% vs 0.7%, chi2=44.7, p=9.88E-11) being the most frequent haplotypes encountered among patients. The classical Caucasian haplotype A1-B8-DRB1*03 was infrequent (7.2%) among the diabetic children. The study highlights the race specificity of HLA association and disease associated HLA haplotypes in T1DM among North Indian children.

摘要

在印度北部的儿童中，对人类白细胞抗原（HLA）编码的1型糖尿病（T1DM）易感性进行了研究。结果显示，患者中HLA - A26、- B8和- B50的患病率显著增加，且该疾病与DRB10301呈强正相关（82.1%对13.9%，卡方=71.3，比值比[OR]=28.3），与DRB102呈负相关（卡方=12.2，P值=38.5）。HLA - DQB10201出现在96.4%的患者中，而异二聚体DQA10501 - DQB10201出现在82.1%的患者中（单剂量占60.7%，双剂量占21.4%），且与健康对照有显著差异（卡方=74.1，P值=6.0×10⁻¹⁰）。除DRB103外，还观察到与DRB109（14.3%对1.3%，卡方=13.4）和DRB104（39.3%对15.6%，卡方=8.39）呈正相关。未观察到HLA与残余胰岛β细胞功能或相关甲状腺自身免疫之间的关联。家系分析显示，在印度北部患有T1DM的儿童中，多个DR3阳性单倍型与疾病相关，其中A26 - B8 - DRB103（25%对3.5%，卡方=16.9，P = 3.96×10⁻⁵）和Ax - B50 - DRB103（25%对0.7%，卡方=44.7，P = 9.88×10⁻¹¹）是患者中最常见的单倍型。经典的白种人单倍型A1 - B8 - DRB1*03在糖尿病儿童中很少见（7.2%）。该研究突出了印度北部儿童T1DM中HLA关联的种族特异性以及与疾病相关的HLA单倍型。