Evaluation of Superoxide Dismutase and Glutathione Peroxidase Enzyme Polymorphisms in Familial Mediterranean Fever Patients

Ali Akbas,Ismail Benli,Leyla Aydogan,Mücahit Egri,Oguzhan Saylan,Fatih Ekici,Bünyamin Kisacik,Sümeyya Akyol,Hüseyin Ozyurt,Semsettin Sahin

doi:10.15197/ejgm.01463

Abstract

Familial Mediterranean Fever (FMF) is a fairly common inflammatory disease in communities with mediterranean origin. It is characterized with autosomal recessive, recurrent short-term episodes of fever, peritoneal, pleural, synovial membrane involvement and skin lesions. The aim of the present study was to investigate possible associations between FMF and Ala-9Val polymorphism of MnSOD and Pro198Leu polymorphism of GPx1. The study included 129 FMF patients who has mutations (E148Q, P369S, F479L, M680I(G/C), M680I(G/A), I692del, M694V, M694I, K695R, V726A, A744S, R761H) in the heterozygous or homozygous form and 95 healthy subjects. To identify MnSOD Ala-9Val and GPx1 Pro198Leu SNPs, genotyping was performed using PCR amplification, and polymorphisms were detected with hybridization probes labeled with fluorescent dyes. Genotype and allele frequencies of Ala-9Val polymorphism of MnSOD and Pro198Leu polymorphism of GPx1 were detected. The MnSOD Val allele frequency is 132 (51.16%) in the FMF and 115 (60.52%) in the control group (p<0.05). The GPx1 Leu allele is 83 (32.17%) in the FMF and 61 (32.11%) in the control group (p=0.988). No significant differences were found between genotype frequencies of GPx1 and MnSOD polymorphisms.According to our findings MnSOD Val allele may be a genetic factor involved in the pathogenesis of FMF. The fact that there are only few studies in literature, we need more patients, other enzyme levels and works about polymorphism to support our study.

Highlights

Familial Mediterranean Fever (FMF) is an autosomal recessively inherited inflammatory disease characterized with recurrent short-term fever attacks, peritoneum, pleura, synovial membrane involvement, and skin lesions [1].The most significant pathologic feature in FMF is recurrent and non-infective acute inflammatory reactions in serosal membranes
We studied 224 patients who applied to the University of Gaziosmanpaşa Health Research and Application Hospital in Tokat region of Turkey with symptoms of FMF. 95 people without FMF mutation were accepted as control group, 129 people who has the FMF mutations (E148Q, P369S, F479L, M680I(G/C), M680I(G/A), I692del, M694V, M694I, K695R, V726A, A744S, R761H) in the heterozygous or homozygous form were chosen as the patient group
The most obvious pathological feature in FMF is the chemotactic activity during episodes of increased polymorphonuclear leukocytes to turn to the affected area caused by repetitive and non-infectious acute inflammatory reactions [15]

Summary

Introduction

Familial Mediterranean Fever (FMF) is an autosomal recessively inherited inflammatory disease characterized with recurrent short-term fever attacks, peritoneum, pleura, synovial membrane involvement, and skin lesions [1].The most significant pathologic feature in FMF is recurrent and non-infective acute inflammatory reactions in serosal membranes. The pain table in FMF disease is created when lysosomal enzyme activation and cell membrane integrity disappears and neutrophil degranulation increases [3]. The duty for SOD enzyme in the antioxidant system is to turn superoxide radical into hydrogen peroxide It is three defined isoforms for which the genomic structure is known. Single nucleotide polymorphism (SNP) that emerged as result of cytosine nucleotide’s displacing the thymine nucleotide (T↔C) was determined in 47th position coding the signal sequence in SOD2 gene. This causes changes in direction of enzyme towards mitochondria, localization and function, . This single-point mutation is called as SOD2 Ala16Val or SOD2 Ala-9Val [7,8]

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