HLA haplotypes associated with type 1 diabetes mellitus in north indian children

• Published in: Human immunology 2004, Vol.65 (1), p.47-53
• Main Authors: Kanga, Uma, Vaidyanathan, Balu, Jaini, Ritika, Menon, Puthezath S.N, Mehra, Narinder K
• Format: Article
• Language: English
• Subjects: Adolescent; Alleles; Autoimmune Diseases - ethnology; Autoimmune Diseases - genetics; Child; Child, Preschool; Diabetes Mellitus, Type 1 - ethnology; Diabetes Mellitus, Type 1 - genetics; Female; Genetic Predisposition to Disease; Genotype; Haplotypes - genetics; HLA Antigens - analysis; HLA Antigens - genetics; HLA haplotypes; HLA-DQ Antigens - analysis; HLA-DQ Antigens - genetics; HLA-DQ beta-Chains; HLA-DR Antigens - analysis; HLA-DR Antigens - genetics; HLA-DRB1 Chains; Humans; India - epidemiology; Infant; Male; Phenotype; residual pancreatic β-cell function; thyroid autoantibodies; Thyroiditis, Autoimmune - ethnology; Thyroiditis, Autoimmune - genetics; type 1 diabetes mellitus
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2003.10.013

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 DRB1*0301 (82.1% vs 13.9%, χ 2 = 71.3, odds ratio [OR] = 28.3) and a negative association with DRB1*02 (χ 2 = 12.2, PF = 38.5). HLA-DQB1*0201 occurred in 96.4% of the patients, whereas the heterodimer DQA1*0501-DQB1*0201 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 (χ 2 = 74.1, p c = 6.0E-10). In addition to DRB1*03, positive association was also observed with DRB1*09 (14.3% vs 1.3%, χ 2 = 13.4) and DRB1*04 (39.3% vs 15.6%, χ 2 = 8.39). No HLA association was observed in relation to residual pancreatic β-cell function or associated thyroid autoimmunity. Family analysis revealed involvement of multiple DR3+ve haplotypes with T1DM in North Indian children with A26-B8-DRB1*03 (25% vs 3.5%, χ 2 = 16.9, p = 3.96E-05) and Ax-B50-DRB1*03 (25% vs 0.7%, χ 2 = 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.