Abstract:

Objective: Familial Mediterranean fever (FMF), caused by the MEFV gene encoding pyrin, is a prevalent monogenic autoinflammatory disease. Nitric oxide (NO), synthesized by nitric oxide synthase (NOS) is a gaseous free radical that modulates the immune response. Endothelial NOS (eNOS) gene variants may affect NO formation. Therefore, we investigated whether the variable eNOS variable number of tandem repeats (VNTR) is involved in the development of FMF. We also examined the association of this variant with clinical findings. Methods: Three hundred seven subjects, including 147 controls and 160 FMF patients, were genotyped for the eNOS VNTR variant using polymerase chain reaction analysis. The patients and controls were compared regarding allele and genotype distribution using the χ2 test. The results were evaluated statistically. Results: 51.9% of the patients had two or more MEFV mutations. The most common mutation in the patients was the homozygous M694V/M694V mutation (25%). The genotype and allele frequencies of the eNOS gene VNTR variant in FMF patients were all compared with those in the healthy controls. A significant difference was found between the patient and control samples for eNOS VNTR genotype distribution. eNOS VNTR homozygous 4a/4a and 4b/4b genotypes were higher in patients than those in the controls (p>0.05). The patients carrying the 4b/4b genotype had higher colchicine usage and responses to colchicine (p˂0.05). There was no statistically significant difference between MEFV mutations and eNOS VNTR genotype distribution in the patients (p>0.05). Conclusion: This study suggests that the VNTR variant of the eNOS gene is associated with FMF formation and some clinical findings in the Turkish population.

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