A 3'-untranslated region variant (rs2289046) of insulin receptor substrate 2 gene is associated with susceptibility to nonalcoholic fatty liver disease.

PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is an increasing global health concern defined by excessive hepatic fat content in the absence of excessive alcohol consumption. Regarding the key role of insulin and insulin resistance in NAFLD, we investigated whether insulin receptor substrate 1 (IRS1) and insulin receptor substrate 2 (IRS2) gene variants were associated with NAFLD risk. METHODS: In this case-control study, 305 subjects including 151 cases with biopsy-proven NAFLD and 154 controls were enrolled. All the subjects were genotyped for IRS1 (rs1801278) and IRS2 (rs2289046) gene variants using PCR-RFLP method. RESULTS: Our findings showed that the IRS2 rs2289046 "GG+AG" genotype compared with "AA" genotype to be a marker of decreased NAFLD susceptibility and the difference remained significant even after adjustment for confounding factors including age, BMI, sex, smoking status, systolic blood pressure, and diastolic blood pressure (P=0.014; OR=0.50, 95%CI= 0.29-0.87). Furthermore, the IRS2 "G" allele was significantly underrepresented in the cases with NAFLD than controls (P=0.026 ; OR=0.62, 95%CI=0.41-0.94). However, no significant difference was found for IRS1 rs1801278 gene variant. CONCLUSIONS: This study suggests, for the first time, that the IRS2 gene rs2289046 variant may play a role in NAFLD susceptibility. Nevertheless, this observation warrants further investigations in other populations.

Adult-onset familial mediterranean Fever in northwestern iran; clinical feature and treatment outcome.

BACKGROUND Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by sporadic, paroxysmal attacks of fever and serosal inflammation. Although the disease usually begins before the age of 20 years, we aimed to evaluate the demography, clinical features and treatment outcome of familial Mediterranean fever in Iranian adult patients above 20 years old. METHODS In this cross-sectional study, adult patients (first attack at the age of >20 years) with a diagnosis of FMF who referred to the gastroenterology and rheumatology Clinics of Ardebil University of Medical Science (situated in north west of Iran) over the period of 2004-2009 were enrolled. FMF diagnosis was based on clinical criteria. RESULTS Forty four FMF patients (30 male and 14 female) with the mean [± Standard Deviation (SD)] age of first attack of 29 ± 7.8 years were enrolled. Abdominal pain (95.5%) and fever (91%) were the most common clinical findings. All of the patients had satisfactorily responded to therapy. Response was complete in 76.7% and partial in 23.3% of the patients. There was no clinical or laboratory evidence of amyloidosis at the time of diagnosis or during follow-up. CONCLUSION Our findings demonstrated that adult-onset FMF in Iran has different characteristics (more common in males, lesser prevalence of arthritis and erysipelas-like erythema, less delay in diagnosis) and treatment outcome (favorable response even to low-dose colchicine) in comparison with the previous data on early onset patients.