Role of HLA class II loci polymorphism in the manifestation of type 1 diabetes in a Bengali Indian patient population

Genet Test Mol Biomarkers. 2013 Jan;17(1):52-61. doi: 10.1089/gtmb.2012.0221. Epub 2012 Nov 2.

Abstract

To assess the contribution of the HLA class II region for susceptibility to type 1 diabetes mellitus (T1DM), we investigated the association of HLA class II alleles-DP, DQ, and DRB1. Here, we present an extensive molecular typing for HLA class II alleles and their haplotypes in a Bengali-speaking Indian population of T1DM patients (n=151) and controls (n=151) from West Bengal. HLA typing was done by DNA sequencing using a 3730 DNA Analyzer. The individual analysis of each gene gave the following alleles to be higher in cases than in controls, thus making them susceptible alleles-DPA1*020103, DPB1*020102, DQA1*050101, DQA1*0201, and DQB1*020101G. Similarly, the following alleles are protective alleles in our study-DPA1*010602, DPB1*040101, DQA1*010201, DQA1*0103, and DRB1*15. Our result confidently establishes that HLA-DP allelic, and its haplotypic, diversity contributes significantly to the risk for T1DM. The DQA1*0103 allele is a novel allele with a significant association with the protection from T1DM. Among the various haplotypes tested, the DQA1*0201:DQB1*020101G, DQA1*050101:DQB1*020101G, and DQA1*0201:DQB1*030101G were the most frequently found in T1DM patients. In India, very few investigations have been undertaken to study the impact of the genetic background on the risk to develop T1DM in its population, where the annual average incidence is 10.5/100,000/year. In conclusion, the present study highlights the genetic effect of HLA haplotypes that contributes to the susceptibility to T1DM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asian People
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology
  • Genetic Loci*
  • Genetic Predisposition to Disease*
  • Genotype
  • HLA-DP alpha-Chains / genetics
  • HLA-DQ Antigens / genetics
  • HLA-DQ beta-Chains / genetics
  • Haplotypes
  • Histocompatibility Antigens Class II / genetics*
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • India
  • Polymorphism, Genetic*

Substances

  • HLA-DP alpha-Chains
  • HLA-DPA1 antigen
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • Histocompatibility Antigens Class II