Association of irisin and FNDC5 rs16835198 G>T gene polymorphism with type 2 diabetes mellitus and diabetic nephropathy. An Egyptian pilot study

• Published in: Gene Vol. 626; pp. 26 - 31
• Main Authors: Khidr, Emad Gamil, Ali, Shawkey Saddik, Elshafey, Mostafa Mahmoud, Fawzy, Olfat Ahmed
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.08.2017
• Subjects: Adult; alleles; blood serum; Browning; Case-Control Studies; Diabetes mellitus; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Diabetic Nephropathies - blood; Diabetic Nephropathies - genetics; Diabetic nephropathy; DNA; Dyslipidemias - etiology; Dyslipidemias - genetics; Egypt; enzyme-linked immunosorbent assay; exercise; Fibronectins - blood; Fibronectins - genetics; genetic polymorphism; genotype; genotyping; health services; Humans; hyperlipidemia; insulin; insulin resistance; Insulin Resistance - genetics; Irisin; Male; morbidity; mortality; noninsulin-dependent diabetes mellitus; patients; Pilot Projects; Polymorphism; Polymorphism, Single Nucleotide; risk reduction; Egypt; T2DM; LDL-C; G; UCP1; DM; WAT; HDL-C; Irisin; SNP; T; Diabetic nephropathy; HbA1c; BMI; eGFR; Diabetes mellitus; PGC-1α; TC; ACR; FNDC5; HOMA-IR; Browning; TG; BAT; FPG; PCR; ELISA; Polymorphism
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2017.05.010

Diabetes mellitus is a fast-growing health problem in Egypt affecting morbidity, mortality and health care resources. Irisin, a new exercise-induced myokine inducing browning of white adipose tissues, has gained a great interest as a potential new target for combating type 2 diabetes mellitus (T2DM) and its complications. In this study, we assessed serum irisin levels in T2DM and diabetic nephropathy to elucidate possible relationships between irisin and metabolic parameters and renal functions. We also investigated, for the first time in Egypt, the association of FNDC5 rs16835198 G>T polymorphism with T2DM, diabetic nephropathy and irisin levels. One hundred type 2 diabetic patients (40 normoalbuminuric and 60 with nephropathy) as well as fifty control subjects were enrolled in this study. Serum irisin and insulin were evaluated by ELISA. Genomic DNA was genotyped for FNDC5 rs16835198 polymorphism using TaqMan genotyping assay. Serum irisin levels were lower in diabetic patients compared to controls and this decrease was more pronounced in diabetic nephropathy. Irisin correlates with metabolic parameters and renal functions. Frequencies of T allele and TT genotype were significantly lower among T2DM and diabetic nephropathy patients compared to controls. Moreover, G allele was associated with elevated insulin resistance and dyslipidemia without effect on circulating irisin levels. In conclusion: T2DM and diabetic nephropathy are associated with decreased levels of irisin. FNDC5 rs16835198 TT genotype associates with decreased risk of T2DM in Egyptians with no effect on renal complications. Also, G allele has insulin desensitizing action with no association with circulating irisin levels. •FNDC5 rs16835198 (G>T) polymorphism provides protection against type 2 diabetes mellitus pathogenesis in Egyptians.•Circulating irisin levels were not affected by FNDC5 rs16835198 (G>T) polymorphism.•FNDC5 rs16835198 G allele was associated with high insulin resistance and dyslipidemia in diabetic patients.•Low serum irisin levels were observed in Egyptian type 2 diabetic patients and diabetic nephropathy patients.•Irisin was correlated with metabolic parameters and renal functions in diabetic patients.