Fibronectin type-III domain-containing protein 5 genetic polymorphism and serum irisin-level change in relation to type-2 diabetes mellitus with diabetic nephropathy

Background Diabetes mellitus (DM) is a group of metabolic disorders that are defined by the presence of levels over a prolonged period. Many complications arise from the long-term standing of hyperglycemia, among which is diabetic nephropathy. Irisin is a newly described exercise-mediated myokine that regulates energy metabolism by converting white into brown fat. Irisin is produced upon cleavage of the precursor plasma membrane protein fibronectin type-III domain-containing protein 5 (FNDC5) and enters the circulation. Irisin was found to be associated with renal functions in chronic kidney disease patients and diabetic nephropathy patients. Patients and methods This study was conducted on 69 Egyptian adult patients (50 females and 19 males), including 53 patients of type-2 diabetics (38 diabetics only and 15 diabetic nephropathy) and 16 healthy controls matched with the patients for the ethnic and demographic characteristics. Serum irisin and insulin were evaluated by enzyme-linked immunosorbent assay. Genomic DNA was genotyped for FNDC5 rs3480 polymorphism using TaqMan genotyping assay. Results We found that irisin level was lower in T2DM (mean±SD=13.11 + 38.14) and diabetic nephropathy (mean±SD=24.99 ± 48.8) patients than controls (mean±SD=13.39 + 26.2) with no significance. The results of our study showed no association between the FNDC5 rs3480 genotype AG [in comparison between control and diabetic nephropathy odds ratio=0.5 (0.1–2.2) with P=0.5]. Also, the AA genotype [odds ratio=2.6 (0.59–11.06), P=0.2] did not show a significant effect on nephropathy in T2DM. Conclusion This study demonstrated that FNDC5 gene rs3480 A>G polymorphism provides a weak risk with no apparent significance of nephropathy on T2DM without effect on serum irisin level. T2DM is associated with decreased levels of circulating irisin, but it was increased in diabetic patients with nephropathy.