Association of HLA class ii alleles and CTLA-4 polymorphism with type 1 diabetes

Abstract EN

Type-1 diabetes mellitus (T1DM) is a progressive complex autoimmune disease in which combinations of environmental as well as genetic factors contribute to T-cell mediated destruction of insulin-secreting β-cells of the pancreas.

HLA class II alleles on chromosome 6p21 [insulin dependent diabetes mellitus 1 (IDDM1)], especially DR and DQ, show strong association with T1DM.

In addition, several studies have suggested that polymorphisms in the CTLA-4 gene (IDDM12) on chromosome 2q33 form part of the genetic susceptibility for type 1 diabetes.

The aim of this study was to analyze HLA alleles of the DQB1 and DRB1 genes using polymerase chain reaction using sequence specific primers (PCR-SSP) technique and to investigate the association of the A49G CTLA-4 polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in Lebanese T1DM patients.

The study was conducted on 39 Lebanese T1DM patients.

Results of HLA typing showed an increased frequency of the HLA-DQB1*0201, HLA-DQB1*0302, HLA-DRB1*0301 and HLA-DRB1*0401 alleles, suggesting risk association and thus can be considered as susceptibility alleles.

On the other hand, strong protection against the disease was conferred by the HLA-DRB1*110101, HLA-DQB1*0301 and HLADQB1*0601 alleles.

RFLP analysis of the A49G polymorphism showed a significant increase in the G allele and GG genotype frequencies in patients, suggesting that CTLA-4 may be considered as a susceptibility gene for the development of T1DM in the Lebanese population.

Analysis of the two polymorphisms showed no detectable association between the two genes.

However, a significant negative association of the G allele with the DQB1*0201 allele was observed.

This might indicate that the two genetic risk factors, namely HLA and CTLA-4, act independently of each other with no additive effect.