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Role of CTLA-4 polymorphism in susceptibility to type 1 diabetes: Results of a family and a case-control study in Southern Tunisia Immunology Department, Habib Bourguiba University Hospital, Sfax ,Tunisia Ferjeni ZOUIDI Pr Hatem MASMOUDI INTRODUCTION Type 1 diabetes (T1D) is characterized by autoimmune destruction of insulin-producing β-cells in the pancreas resulting from the action of environmental factors on genetically predisposed individuals β cells Destruction is caused by the infiltration of islets of Langerhans by CD8+ and CD4+ T lymphocytes The HLA region account for approximately 50% of the genetic determination of the T1D. The other half is made up of multiple genes, each having a limited individual impact on genetic susceptibility OBJECTIVE Studying the role of two SNPs (CT/60 and AG/49) CTLA-4 gene in susceptibility to T1D. SUBJECTS AND METHODS Subjects Family study: 56 families (25 multiplex each comprising at least 2 diabetics and 31 simplex) including 87 with type 1 diabetes and 178 of their first-degree relatives were analysed Case-control study The case-control study has been performed on the 56 index cases (35 men, 21 women ;median onset age 13,10 ± 4,5 years; range, 2 to 45 ) and 120 healthy control subjects (12 men and 108 women; median onset age 42 years; range, 25 to 65) with no family history of diabetes Methods PCR-RFLP Statistical study FBAT( family based association test) was applied to identify alleles and haplotypes preferentially transmitted from heterozygous parents to affected offspring X ² test was used to compare categorical data between patients with type 1 diabetes and controls RESULTS Table 1: Distribution of alleles frequencies (%), haplotype and FBAT results Allèles/haplotypes A G C T AT GC AC GT Frequencies (%) 72% 28% 54% 46% Z -1.23 1.23 1.51 -1.51 p 2.21 2.21 0.13 0.13 41% 29.2% 28.5% 01.4% -1.49 1.54 0.15 - 0.13 0.12 0.87 - Z is significant if its value is ≥ 1.96 or ≤ -1.96 with a p less than 0.05 FBAT analysis showed no preferential transmission of both alleles and haplotypes from parents to affected children for the AG/49 and CT60 polymorphisms (p=2.21,p=0.13 respectively) Table 2: Genotype and allele distribution of the CTLA-4 CT60 and AG/49 SNP in DT1 patients and controls. CT60 AG/49 Alleles/Genotypes C T CC CT TT A G AG GG AA controls(%) 55.83 44.16 37.5 36.66 25.83 68.33 31.66 10.00 43.33 46.66 DT1(%) 55.35 44.64 30.35 50.00 19.64 p 0.93 0.93 0.35 0.93 0.36 69.64 30.35 07.81 39.28 50 0.80 0.80 0.61 0.88 0.68 Discussion For the case-control study no significant differences (p=0.80, p=0.93 respectively) was detected for the markers CTLA-4 CT60 and AG/49 respectively. Our study indicate that the 49A/G and CT60 polymorphisms of the CTLA-4 gene are not associated with increased susceptibility to DT1 in southern Tunisia. This result is consistent with that reported by others family studies [Marron MP et al;1997Angel B et al;2009]. Furthermore other case-control studies in Great Britain, Northern Ireland, China, and Slovakia found no association between polymorphism AG/49, CT60 and T1D[Nisticò L et al;1996-Dallos T et al;2008]. However, the results of many case-control studies showed a great association between the two markers and DT1[Benmansour J et al;2010-Mayans S et al;2007]