title: Association of HLA class II alleles and CTLA-4 polymorphism with type 1 diabetes.
abstract: 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-DQB1FNx010201, HLA-DQB1FNx010302, HLA-DRB1FNx010301 and HLA-DRB1FNx010401 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-DRB1FNx01110101, HLA-DQB1FNx010301 and HLADQB1FNx010601 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 DQB1FNx010201 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.
authors.affiliation: Department of Biochemistry, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
authors.forename: Rana J
authors.initials: RJ
authors.lastname: Ei Wafai
authors.forename: Hania Nakkash
authors.initials: HN
authors.lastname: Chmaisse
authors.forename: Rajaa F
authors.initials: RF
authors.lastname: Makki
authors.forename: Hana
authors.initials: H
authors.lastname: Fakhoury
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D018912:Arabs / Q000235:genetics; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007861:Lebanon / Q000453:epidemiology; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains