title: 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.
abstract: 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.
authors.affiliation: Department of Neurogenetics, Iranian Centre of Neurological Research, Tehran.
authors.forename: A
authors.initials: A
authors.lastname: Sayad
authors.forename: M T
authors.initials: MT
authors.lastname: Akbari
authors.forename: M
authors.initials: M
authors.lastname: Pajouhi
authors.forename: F
authors.initials: F
authors.lastname: Mostafavi
authors.forename: M
authors.initials: M
authors.lastname: Zamani
mesh_terms: D000293:Adolescent; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques / Q000379:methods; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007492:Iran / Q000453:epidemiology; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D015203:Reproducibility of Results; D012307:Risk Factors; D020539:Sequence Analysis, Protein; D044465:White People / Q000235:genetics
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains