Deniz Erol

Familial Mediterranean Fever: A Retrospective Clinical and Molecular Study in the East of Anatolia Region of Turkey

Familial Mediterranean Fever (FMF) is an autoinflammatory periodic disorder. We aim to identify the distribution and the frequency of the Mediterranean Fever (MEFV) gene mutations in the east of Anatolia in Turkey and perform a genotype/phenotype correlation in the patients’ cohort. The study was carried out on 415 clinically diagnosed Turkish FMF patients and 103 healthy controls. The tested individuals were screened for the most common twelve MEFV mutations. The most important features were the predominance of the M694V and E148Q mutations in patient group and the earlier of onset of the disease in M694V mutation carriers compared with the carriers of other mutations (P=0.00). We discuss the high frequency of E148Q mutations in patient group compared with controls, genetic counseling in intermarriage families and the variations in mutation frequency according to regions of Turkey.

Investigating paraoxonase-1 gene Q192R and L55M polymorphism in patients with renal cell cancer.

Increased oxidative stress can help promote carcinogenesis, including development of renal cell carcinoma. The enzyme protects low-density lipoproteins from oxidation and can be a factor in this process. PON1 Q192R and L55M paraoxonase gene polymorphisms were assessed in 60 renal cell carcinoma patients and 60 healthy controls. Genotypes were examined by PCR; the restriction enzyme AlwI was used to examine the Q192R polymorphism and Hsp92II for the L55M polymorphism. Significant differences in the PON1 Q192R polymorphism were found between patients and controls. The Q allele was more frequent in the patient group than in controls, while the R allele was more frequent in the control group. No significant differences were found in the L55M polymorphism. Additionally, there were no significant differences in L and M allele frequencies. We conclude that the R allele may protect against renal cell carcinoma.

Decreased MEFV gene expression in rheumatoid arthritis patients

Rheumatoid arthritis (RA) is a major cause of adult chronic inflammatory arthritis and an autoimmune disease of unknown etiology in which the inflammatory pathology involves T cell activation. Genetic mutations in the Mediterranean fever (MEFV) gene, encoding pyrin, influence the severity of RA, but the underlying mechanisms are not completely understood. In this study, we investigated whether the full-length MEFV gene (MEFV-fl) and the exon 2-deleted splice isoform (MEFV-d2) expression are associated with or responsible for the clinical conditions of RA. This study include 47 patients with RA and 47 age- and gender-matched healthy controls. Quantitative real-time polymerase chain reaction analysis was performed to examine transcriptional changes in MEFV gene expression from peripheral blood samples. Reverse transcription-polymerase chain reaction of peripheral blood cells revealed the downregulation of MEFV-fl mRNA in non-treated patients compared with healthy controls and treated patients. MEFV-d2 expression was not different between groups. This is the first study to investigate the expression of MEFV transcript in RA. Deregulation of the MEFV gene is likely to result in uncontrolled inflammation as observed in RA. Therefore, downregulation of MEFV-fl may be involved in the pathogenesis of early-stage RA and treatment and may ameliorate MEFV-fl expression.

Mediterranean fever gene mutation analysis in infertile Turkish males.

Male infertility is a common barrier that prevents successful conception. There have been reports of azoospermia in men with familial Mediterranean fever, some of whom had not been treated with colchicine. Variation in this disorder could be a risk factor for amyloidosis associated with azoospermia. We determined the frequency of 6 of the most common Mediterranean fever gene mutations, M680I, M694V, M694I, V726A, P369S, and A744S, in 74 infertile men, 155 men diagnosed with familial Mediterranean fever and 55 healthy fertile men in eastern Turkey. All three groups were screened for the 6 mutations using an amplification refractory mutation system and restriction fragment length polymorphism methods. Allelic frequencies were 2.7% for M694V and 1.35% for V726A in the infertile patient group and 1.8% for M694V and 1.8% for V726A in healthy subjects. Other mutations were not detected in patients or controls. The mutation frequency was not found to be significantly higher in infertile patients when compared with healthy fertile male controls. To our knowledge, this is the first study to determine the frequency of Mediterranean fever gene mutations in infertile male and the infertility rate of male patients with familial Mediterranean fever.

Protein Tyrosine Phosphatase Non-receptor 22 Gene C1858T Polymorphism in Patients with Coexistent Type 2 Diabetes and Hashimoto's Thyroiditis.

BACKGROUND A protein tyrosine phosphatase non-receptor type 22 (PTPN22) C1858T gene polymorphism has been reported to be associated with both Type 2 diabetes mellitus (T2DM) and Hashimotos thyroiditis (HT) separately. However, no study has been conducted to explore the C1858T polymorphism in T2DM and HT coexistent cases up to now. AIMS The study aimed to determine whether a relationship exists or not between the PTPN22 C1858T polymorphism and this coexistent patient group. STUDY DESIGN Case-control study. METHODS Peripheral blood samples from 135 T2DM patients, 102 patients with coexistent T2DM+HT, 71 HT patients and 135 healthy controls were collected into ethylenediaminetetraacetic acid (EDTA) anticoagulant tubes and genomic DNA was extracted. The PTPN22 C1858T polymorphism was analyzed using polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) methods. RESULTS Statistically significant differences were not observed between the patient and control groups. This study demonstrated a statistically significant association between both the CT genotype and the T allele in the female patient group with coexistent T2DM+HT (CT genotype: p=0.04; T allele: p=0.045) with a statistically significant association between the CT genotype and the mean values of body mass index (BMI) and free T3 levels (FT3) (BMI: p=0.044 and FT3: p=0.021) that was detected in the patient group with coexistent T2DM+HT. The minor genotype TT was observed in none of the groups in this study. The CT genotype frequency was [number (frequency): 5 (3.8%), 7 (6.86%), 5 (7.04%), 3 (2.22%), while the T allele frequency was 5 (1.86%), 7 (3.44%), 5 (3.53%) and 3 (1.12%)] in the T2DM, T2DM+HT, HT and control groups, respectively. CONCLUSION Our data suggest that the PTPN22 1858T allele and the CT genotype are associated with increased risk in female patients for coexistent T2DM+HT. The CT genotype was associated with high mean BMI and free T3 values in the patient group with coexistent T2DM+HT. These results demonstrate that T allele carriers were more often in the T2DM+HT group than in the T2DM group. Therefore, the combination of T2DM and HT with female gender may have higher T allele carriage in comparison to the T2DM only and male groups.