title: The role of IL-4 gene 70 bp VNTR and ACE gene I/D variants in Familial Mediterranean fever.
abstract: Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. It is an autosomal recessive disease caused by mutations in the MEFV (MEditerranean FeVer) gene. Patients with similar genotypes exhibit phenotypic diversity. As a result, the variations in different genes could be responsible for the clinical findings of this disease. In previous studies genes encoding Angiotensin-Converting Enzyme (ACE) and IL-4 (Interleukin-4) were found to be associated with rheumatologic and autoimmune diseases. In the present study we hypothesized whether ACE I/D or IL-4 70 bp variable tandem repeats (VNTR) genes are associated with FMF and its clinical findings in Turkish patients. Genomic DNA obtained from 670 persons (339 patients with FMF and 331 healthy controls) was used in the study. Genotypes for an ACE gene I/D polymorphism and IL-4 gene 70 bp VNTR were determined by polymerase chain reaction with specific primers. To our knowledge, this is the first study examining ACE gene I/D polymorphism and IL-4 gene 70 bp VNTR polymorphism in FMF patients. As a result, there was a statistically significant difference between the groups with respect to genotype distribution (p<0.001). According to our results, ACE gene DD genotype was associated with an increased risk in FMF [p<0.001; OR (95%): 7.715 (4.503-13.22)]. When we examined ACE genotype frequencies according to the clinical characteristics, we found a statistically significant association between DD+ID genotype and fever (p=0.04). In addition IL-4 gene P1P1 genotype was associated with FMF (p<0.001). We propose that D allele or DD genotype of ACE gene and P1 allele or P1P1 genotype of IL-4 gene may be important molecular markers for susceptibility of FMF.
authors.affiliation: Gaziosmanpaşa University, Faculty of Medicine, Department of Medical Biology, Tokat, Turkey. Electronic address: serbulent.yigit@gmail.com.
authors.forename: Serbülent
authors.initials: S
authors.lastname: Yigit
authors.affiliation: Ondokuz Mayis University, Faculty of Medicine, Department of Medical Biology and Genetics, Section of Medical Genetics, Samsun, Turkey. Electronic address: stural@omu.edu.tr.
authors.forename: Sengul
authors.initials: S
authors.lastname: Tural
authors.affiliation: Ondokuz Mayis University, Faculty of Medicine, Department of Medical Biology and Genetics, Section of Medical Genetics, Samsun, Turkey. Electronic address: akintekcan@hotmail.com.
authors.forename: Akın
authors.initials: A
authors.lastname: Tekcan
authors.affiliation: Gaziosmanpaşa University, Faculty of Medicine, Department of Internal Medicine, Tokat, Turkey. Electronic address: turtasliyurt@hotmail.com.
authors.forename: Turker
authors.initials: T
authors.lastname: Tasliyurt
authors.affiliation: Gaziosmanpaşa University, Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Tokat, Turkey. Electronic address: ainanir@gmail.com.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Inanir
authors.affiliation: Gaziosmanpaşa University, Faculty of Medicine, Department of Internal Medicine, Tokat, Turkey.
authors.forename: Süheyla
authors.initials: S
authors.lastname: Uzunkaya
authors.affiliation: Ankara University, Veterinary Faculty, Department of Biochemistry, Ankara, Turkey. Electronic address: gorkemkismali@yahoo.com.
authors.forename: Gorkem
authors.initials: G
authors.lastname: Kismali
mesh_terms: D000328:Adult; D003598:Cytoskeletal Proteins / Q000235:genetics; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics*; D009154:Mutation; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000071198:Pyrin; D014421:Turkey
chemical_list: D003598:Cytoskeletal Proteins; C508598:IL4 protein, human; C000604192:MEFV protein, human; D000071198:Pyrin; D015847:Interleukin-4; D007703:Peptidyl-Dipeptidase A
keywords: ACE gene; Familial Mediterranean fever; IL-4 gene; Polymorphism