title: Analysis of cytotoxic T lymphocyte antigen-4 (CTLA-4) promoter -318C/T and +49A/G gene polymorphisms in Turkish patients with familial Mediterranean fever.
abstract: Either the role of the adaptive immune system or the interaction between innate and adaptive immune systems in familial Mediterranean fever (FMF) is not clear so far. So, we planned to search for the interaction between the innate and adaptive immune systems in the pathogenesis of FMF by investigating polymorphism for CTLA-4 gene, which plays a role in controlling antigen presentation to T cells. We also aimed to investigate whether there is an association between -318C/T and +49A/G polymorphisms in the CTLA-4 gene and the main clinical features of the disease. 75 FMF patients and 179 controls were studied. Polymorphism was detected by the PCR-RFLP technique. The CT genotype and T allele frequencies of the -318C/T polymorphism and the haplotype frequency for the -318T/+49A in the CTLA-4 gene were higher in the FMF (21.3, 21.3, and 10.7 %) when compared with the controls (10.6, 10.6, and 5.3 %; P = 0.029, 0.044, and 0.029). However, these differences did not reach a statistically significant level after the Bonferroni correction. A significant linkage disequilibrium was found between the -318C/T and +49A/G polymorphisms in the CTLA-4 gene (D' = 0.997, r(2) = 0.027, P = 0.0002). Genotype and carrier frequencies of the CTLA-4 gene +49A/G polymorphism were not significantly different between FMF patients and healthy controls. No association was found between the studied polymorphisms and the main clinical features of the disease. Our findings suggest that although not statistically significant, higher frequencies of CTLA-4 gene -318CT genotype, T allele, and -318T/+49A haplotype in FMF patients may be related to the non-autoimmune pathogenesis of FMF.
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey. rgunesacar@hotmail.com
authors.forename: Ramazan
authors.initials: R
authors.lastname: Gunesacar
authors.forename: Eren
authors.initials: E
authors.lastname: Erken
authors.forename: Suzan
authors.initials: S
authors.lastname: Dinkci
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D060908:CTLA-4 Antigen / Q000235:genetics*; D010505:Familial Mediterranean Fever / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014421:Turkey; D055815:Young Adult
chemical_list: D060908:CTLA-4 Antigen