Diverse human leukocyte antigen association of type 1 diabetes in north India

Abstract

Highlights• Type 1 diabetes (T1D) in north India is strongly associated with HLA-DRB1*03 haplotypes. • The association between HLA-DRB1*04 and T1D in north India differs from that in south India and in Caucasians. AbstractBackground: Type 1 diabetes (T1D) is a complex disease, with involvement of various susceptibility genes. Human leukocyte antigen (HLA) on chromosome 6p21 is major susceptibility region. This study examined genetic association of HLA genes with T1D.Methods: The study recruited 259 T1D patients and 706 controls from north India. PCR-SSP and LiPA were used to type HLA Class I and II alleles. Results: At HLA Class I locus, HLA-A*02, A*26, B*08 and B*50 were significantly increased in patients vs controls (39.8% vs 28.9% [Bonferroni-corrected P {P c } = 0.032], 24.7% vs 9.6% [P c = 4.83 × 10 −8 ], 37.2% vs 15.7% [P c = 1.92 × 10 −9 ], and 19.4% vs 5.5% [P c = 4.62 × 10 −9 ], respectively). Similarly, in Class II region, DRB1*03 showed a strong positive association with T1D (78.7% vs 17.5% in controls; P = 1.02 × 10 −9 ). Association of DRB1*04 with T1D (28.3% vs 15.5% in controls; P c = 3.86 × 10 −4 ) was not independent of DRB1*03. Negative associations were found between T1D and DRB1*07, *11, *13, and *15 (13.8% vs 26.1% in controls [P c = 0.00175], 3.9% vs 16.9% in controls [P c = 6.55× 10 −6 ], 5.5% vs 21.6% in controls [P c = 2.51 × 10 −7 ], and 16.9% vs 43.9% in controls [P c = 9.94× 10 −10 ], respectively). Compared with controls, patients had significantly higher haplotype frequencies of A

Type 1 Diabetes and Autoimmune Thyroid Disease—The Genetic Link

“…Although certain HLA Class II molecules may initiate the CD4 + T-cell mediated autoimmune response, HLA Class I molecules induce autoantigen-specific CD8 + T cell-mediated cytotoxicity, explaining with a plausible immunological rationale, and the genetic association of both HLA Class I and Class II molecules with glandular autoimmunity. This combination has synergistic and complementary effects on various stages of the autoimmune response ( 73 ).…”

“…While in Northern India HLA-DRB1*04 and DRB1*03 were increased in patients with T1D, only the DRB1*03 allele was strongly associated with T1D and DRB1*04 was only increased in combination with DRB1*03. In Southern India however, both DRB1*03 and DRB1*04 contributed equally towards disease predisposition ( 73 ).…”

Childhood and adolescent diabetes in the Indian subcontinent: A glass half full

“…In contrast, the association with HLA-DRB1*04/DQB1*03 (DR4/DQ8) is considerablyweaker. 12 Negative associations were noted with DRB1*07, 11, 13, and 15. There is currently only preliminary information on Indians regarding other genetic loci predisposing to T1DM, such as INS, CTLA4, PTPN22, IL2RA, and others.…”

“…The HLA associations in north Indian patients show the HLA‐DRB1*03/DQB1*02 (DR3/DQ2) to be strongly associated with T1DM, as in their European counterparts. In contrast, the association with HLA‐DRB1*04/DQB1*03 (DR4/DQ8) is considerablyweaker 12 . Negative associations were noted with DRB1*07, 11, 13, and 15.…”

HLA‐A*33:03:01:06 allele identified in an individual from the Kashmiri Brahmin population of North India

“…HLA-A*33 is reported with a frequency of 9.1% among North Indians. 2 In this article, we describe the identification of a new allele, HLA-A*33:03:01:06 in a North Indian individual from a study evaluating genomic profile of Kashmiri Brahmin population.…”