title: SNPs in FNDC5 (irisin) are associated with obesity and modulation of glucose and lipid metabolism in Saudi subjects.
abstract: BACKGROUND
  Irisin is a recently identified myokine that plays an important role in preventing obesity and insulin resistance. We investigated whether the common FNDC5 (irisin precursor) gene variants influence susceptibility to obesity and type 2 diabetes (T2D) and verified the impact of FNDC5 gene variants on serum irisin levels, glucose and lipid metabolism in a Saudi population.
  
  
  METHODS
  Genomic DNA from 814 (394 T2DM and 414 controls) subjects were genotyped for the five common SNPs (rs3480A/G, rs1746661G/T, rs1298190A/G, rs726344A/G and rs1570569G/T) of the FNDC5 gene using the TaqMan genotyping assay. Biochemical parameters and hematic concentrations of irisin and insulin as well as anthropometric indices were collected.
  
  
  RESULTS
  Serum irisin levels were higher in T2DM patients compared to controls (p < 0.0001). Analyses of FNDC5 SNPs showed that: 1) The rs3480 GG associates with decreased risk of obesity (p = 0.005; odds ratio: 0.48) and lower body mass index (BMI) values (p = 0.03). In addition, GGAAG was identified as the protective haplotype against risk of obesity (p = 0.001; odds ratio: 0.23). 2) The rs1746661 G allele associates with higher triglyceride (TG) levels (p = 0.019). 3) The rs157069 TT genotype associates with higher fasting insulin (p = 0.029) and HOMA-IR (p = 0.002) as well as with lower circulating irisin levels (p = 0.016).
  
  
  CONCLUSIONS
  SNPs in FNDC5 gene correlates with obesity and glucose-lipid metabolism possibly because they modulate the serum levels of irisin.
authors.affiliation: Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, PO Box, 2455, Riyadh, 11451, Saudi Arabia. aldaghri2011@gmail.com.|Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia. aldaghri2011@gmail.com.
authors.forename: Nasser M
authors.initials: NM
authors.lastname: Al-Daghri
authors.affiliation: Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, PO Box, 2455, Riyadh, 11451, Saudi Arabia.|Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Abdul Khader
authors.initials: AK
authors.lastname: Mohammed
authors.affiliation: Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, PO Box, 2455, Riyadh, 11451, Saudi Arabia.|Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Omar S
authors.initials: OS
authors.lastname: Al-Attas
authors.affiliation: Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, PO Box, 2455, Riyadh, 11451, Saudi Arabia.|Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Osama E
authors.initials: OE
authors.lastname: Amer
authors.affiliation: Department of Physiopathology and Transplantation, University of Milan, Milan, 20090, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
authors.affiliation: School of Biological Sciences, University of Southampton, Southampton, SO17 1BJ, UK.
authors.forename: Amal
authors.initials: A
authors.lastname: Alenad
authors.affiliation: Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, PO Box, 2455, Riyadh, 11451, Saudi Arabia.|Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Majed S
authors.initials: MS
authors.lastname: Alokail
mesh_terms: D000328:Adult; D018912:Arabs / Q000235:genetics; D001786:Blood Glucose / Q000235:genetics*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012529:Saudi Arabia
chemical_list: D001786:Blood Glucose; C577593:FNDC5 protein, human; D005353:Fibronectins
keywords: Insulin; Irisin; Obesity; SNPs; Triglyceride; Type 2 diabetes