The Role of IL-4 Gene 70bp 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 70bp 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 70bp 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 70bp 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 P<inf>1</inf>P<inf>1</inf> genotype was associated with FMF (p<0.001). We propose that D allele or DD genotype of ACE gene and P<inf>1</inf> allele or P<inf>1</inf>P<inf>1</inf> genotype of IL-4 gene may be important molecular markers for susceptibility of FMF. © 2014 Elsevier Ltd.