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01 November 1996

Insulin dependent diabetes mellitus (type 1) analysis of HLA DQA1(52) and HLA DQB1(57) codons

Henryk W Witas, Jerzy Bodalski, Krystyna Jędrychowska-Dańska, Marcin Różalski, Wojciech Mlynarski, Dorota Cedzyńska, Ewa Brzeziańska

Med Sci Monit 1996; 2(6): CR734-739 :: ID: 500135

Abstract

Allele-specific amplification PCR method (ASA-PCR) allows to genotype possible codons at HLA-DQA152, and HLA-DQB157, locations which in turn allows the definition of expressed amino acid. The analysis of codon variants frequency was performed in insulin dependent diabetes mellitus (IDDM) children (n=50) and control subjects (n=50) of Polish origin. Aliphatic and hydrophobic amino acids residues (phenotypes: Val/Ala and Ala/Ala) were found to occur significantly more frequently at DQ&β57, in IDDM children (74%) than in control subjects (18%); RR=12.96. The dominant protective effect of DQβAsp57, is suggested. Codons for Asp/Asp were not found in IDDM children while they were exhibited by 28% of controls (RR=0.025). Simultaneous typing of both codons revealed that DQαArg52+/DQβAsp57-, accompany the IDDM phenotype much more frequently than the physiological one (68% v. 22% RR=7.53). The analysis of a number of susceptibility (αArg52+,/βAsp57-,) heterodimers which can occur in one child revealed that the exclusive expression of such dimers (100%) and presence of half of them (50%) was more frequently in the IDDM group (RR= 4.47 and 2.57, respectively). The lack of αArg52+,/βAsp57-, dimers or their involvement only at rate of 1/4 (25%) is characteristic of the control group (RR=0.173 calculated for both cases together). The presented results are the first qualitative and quantitative analysis of studied polymorphism of genes coding the dimeric protein which presents antigen on the cell surface. This preliminary studies contribute to a detailed analysis of allelic variants in the Polish population which is necessary in the evaluation of children belonging to the group a high risk for IDDM. Supported by grant KBN No. 4 P05E 053 08

Keywords: insulin dependent diabetes mellitus, IDDM, HLA, DNA amplification, Genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750