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The influence of the HLA‐DRB, HLA‐DQB and polymorphic positions of the HLA‐DRβ1 and HLA‐DQβ1 molecules on risk of Iranian type 1 diabetes mellitus patients
Author(s) -
Sayad A.,
Akbari M. T.,
Pajouhi M.,
Mostafavi F.,
Zamani M.
Publication year - 2012
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/j.1744-313x.2012.01116.x
Subject(s) - human leukocyte antigen , medicine , immunology , hla dq , diabetes mellitus , type 1 diabetes , antigen , genetics , allele , biology , haplotype , gene , endocrinology
Summary Type 1 Diabetes mellitus (T1D) is an autoimmune and multifactorial disease. HLA‐DRB1 and DQB1 loci have the strongest association with T1D. This study aimed at investigating (i) susceptibility or protection of alleles, genotypes and haplotypes of HLA‐DRB1 and DQB1 loci; and (ii) highly polymorphic amino acid residues of HLA‐DRβ1 and DQβ1 in 105 Iranian T1D patients and 100 controls. The results indicated that DRB1*04:01, 03:01, DQB1*03:02, 02:01 alleles, DRB1*03:01/04:01, 03:01/13:03, DQB1*02:01/03:02 genotypes, DRB1*04:01‐DQB1*03:02, DRB1*03:01‐DQB1*02:01, DRB1*07:01‐DQB1*03:03 haplotypes had positive association with T1D. In contrast, HLA‐DRB1*15:01, 13:01, DQB1*03:01, 06:01 alleles, DRB1*11:01/15:01, DQB1*03:01/06:01, 03:01/05:01 genotypes and DRB1*15:01–DQB1*06:01, DRB1*11:01–DQB1*03:01 haplotypes had negative association with T1D. Analysis of amino acid sequence of HLA‐DRβ1 and DQβ1 revealed that DRβ1 Lys71+ and DQβ1 Asp57− were significantly more frequent in patients than in controls and had a positive effect in the development of T1D. Haplotype analysis demonstrated that HLA‐DRB1 Lys71+ allele provided major susceptibility for T1D, and DQβ1 Asp57− had an additive effect. We designed an allele‐specific primer to develop an easy, quick and cost‐benefit method to detect the DRβ1 Lys71+ . This method can identify all 114 DRB1 alleles encoding DRβ1 Lys71+ by three PCR reactions. The PcPPV and PcNPV were also calculated to determine the impact of HLA genotype testing at amino acid positions. It showed that the DRβ1 Lys71+/+ genotype carrier had 1% absolute risk of developing T1D.