SP036THE FREQUENCY OF MEFV GENE MUTATIONS IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE PATIENTS

Abstract

Introduction and Aims: Autosomal dominant polycystic kidney disease (ADPKD) is the most common of the inherited renal cystic diseases and constitutes 10% of the end stage renal disease population. Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of polyserositis and fever which has an autosomal recessive inheritance. ADPKD is caused by PKD1 gene mutations in 85% of the cases which is identified in chromosome 16p13.3 and 46 exons, likewise FMF is caused by mutations in the MEFV gene which is located on the same chromosome region 16p13.3, but slightly different 2, 10 exons. The episodes of fever and abdominal pain in ADPKD patients are generally believed to be arised from the renal and urinary complications. However, these symptoms maybe be the sign of serous inflammation in patients with ADPKD and FMF. And these individuals may have increased frequency of MEFV gene mutations carriage in risk groups. Therefore, we aimed to evaluate the frequency of MEFV gene mutations in ADPKD patients with abdominal pain, fever or arthritis attacks who may have coexistence of FMF. Methods: Twenty-four ADPKD patients with the medical history of recurring and self-limited episodes of fever, abdominal pain or arthritis with inflammation, of one or several serous ( peritoneum, pleura, pericardium) attending consecutively to our hospitals were included in the study. MEFV gene mutations were analyzed. Results: In this study, twenty-four ADPKD patients (male/female:14/10) were included. The mean age was 43.2 years. In 7 ADPKD patients, MEFV gene mutations were determined with 8 allelic variants. The allelic variants were heterogenous M694V (3/48, 6%), heterogenous E148Q (2/48, 4%), heterogenous V726A, heterogenous P369S, and compound heterogenous M680I (G/C). According to Tel-Hashomer criteria, three patients with higher than 1000 mg proteinuria had diagnosed as FMF and amyloidosis by endoscopic biopsies. Two of them were heterogenous M694V and one of them was compound heterogenous M680I (G/C). One of the 3 patients with amyloidosis (heterogenous M694V) had a living-donor renal transplantation at the age of 48 years. In the literature, a high frequency of MEFV carriers in the healthy Turkish population (20%) was reported. In the current study, we found the prevalence of total allelic MEFV variants to be the same in ADPKD patients (17%) compared with healthy Turkish subjects (p > 0.05). Conclusions: Although, there was no increase in frequency of MEFV gene mutations in ADPKD patients compared with the healthy controls in Turkish population three patients had diagnosed as FMF and amyloidosis. There may be a coexistence of this two common genetic disorders, especially, MEFV gene mutations may play a specific or an occult role in the development of FMF related amyloidosis in ADPKD patients. Further large trials are needed to show if the synchrony of these two disorders can simply be explained as incidental or not.