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The influence of polymorphic positions of the HLA-DRβ1 and HLA-DQβ1 molecules on risk of T1D in Iranian population

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Year: 2012
COI code: CIGS12_0967
Paper Language: English

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Authors The influence of polymorphic positions of the HLA-DRβ1 and HLA-DQβ1 molecules on risk of T1D in Iranian population

  Arezou Sayad - Department of Medical Genetics, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran
  Mehdi Zamani - Department of Neurogenetics, Iranian Centre of Neurological Research , Tehran University of Medical Sciences, Tehran, Iran- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  Mohammad Taghi Akbari - Department of Medical Genetics, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran
  Anooshirvan Kazemnejad - Department of Biostatistics, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran

Abstract:

Type 1 Diabetes mellitus (T1D) is a chronic autoimmune and multifactorial disease. The HLA-DRB1 and DQB1 loci have the strongest association with T1D. Various HLA-DRB1 and DQB1 alleles encode different amino acids in critical positions of HLA-DRβ1 and DQβ1 molecules. We investigated highly polymorphic amino acid residues of HLA-DRβ1 and DQβ1 to determine their susceptibility or protective effect in 105 Iranian T1D patients and 100 controls. Analysis of amino acid sequence of HLA-DRβ1 and DQβ1 revealed that DRβ1(Lys71+) and DQβ1(Asp57)- were significantly more frequent in patients than controls and had a positive effect in development of T1D. The homozygous DRβ1(Lys71+/+) and DQβ1(Asp57-/-) genotype provided the highest risk for TD1. Haplotype analysis of our data demonstrated that HLA-DRB1(Lys71+) allele provide major susceptibility for T1D and DQβ1(Asp57-) has an additive effect. Since DRB1(Lys71+) allele has a crucial role for developing T1D, we designed allele-specific primers to develop an easy, quickly and cost-benefit method to detect the DRβ1(Lys71+). Indeed, we can identify all 114 DRB1 alleles encoding DRβ1(Lys71+) by three simple PCR reactions. In conclusion our findings suggest that the DRβ1(Lys71+) has the main influence on the susceptibility of the Iranian T1D patients and the effect of the DQβ1(Asp57-) on the disease risk is additive. Furthermore, our simple method for detecting high risk DRβ1(Lys71+) allele is very valuable method to identifying at risk individuals for T1D.

Keywords:

Type 1 diabetes; T1D; DRB1; DQB1; DRβ1(Lys71); DQβ1(Asp57); amino acid; genetic risk

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COI code: CIGS12_0967

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Sayad, Arezou; Mehdi Zamani; Mohammad Taghi Akbari & Anooshirvan Kazemnejad, 2012, The influence of polymorphic positions of the HLA-DRβ1 and HLA-DQβ1 molecules on risk of T1D in Iranian population, 12th Congress of Iranian Genetics Society, تهران, انجمن ژنتيك ايران, https://www.civilica.com/Paper-CIGS12-CIGS12_0967.htmlInside the text, wherever referred to or an achievement of this article is mentioned, after mentioning the article, inside the parental, the following specifications are written.
First Time: (Sayad, Arezou; Mehdi Zamani; Mohammad Taghi Akbari & Anooshirvan Kazemnejad, 2012)
Second and more: (Sayad; Zamani; Akbari & Kazemnejad, 2012)
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Type: state university
Paper No.: 25939
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