title: Irisin-encoding gene (FNDC5) variant is associated with changes in blood pressure and lipid profile in type 2 diabetic women but not in men.
abstract: BACKGROUND
  Irisin has recently been described as a novel myokine, which reduces visceral obesity and improves glucose metabolism in mice. Thus, polymorphisms in the gene encoding irisin, fibronectin type III domain containing 5 (FNDC5), may be associated with type 2 diabetes mellitus (T2DM) and related disorders. However, to date, no study has investigated the association between FNDC5 polymorphisms and susceptibility to T2DM.
  
  
  OBJECTIVE
  To investigate the association of FNDC5 rs3480 (A/G) and rs1746661 (G/T) polymorphisms, alone or in combination, with T2DM and its clinical features.
  
  
  METHODS
  We analyzed 1006 T2DM patients and 434 nondiabetic subjects. Polymorphisms were genotyped by real-time PCR using TaqMan MGB probes. Haplotypes constructed from the combination of rs1746661 and rs3480 polymorphisms were inferred using the Phase 2.1 program.
  
  
  RESULTS
  Genotype, allele and haplotype frequencies of rs1746661 and rs3480 polymorphisms did not differ significantly between nondiabetic subjects and T2DM patients. Women with T2DM carrying the G allele of rs3480 showed increased HbA1c levels compared with A/A carriers, adjusted for age. The T allele of rs1746661 was associated with increased systolic blood pressure, total cholesterol and LDL-cholesterol and decreased HDL-cholesterol in women with T2DM, adjusted for covariates. Moreover, prevalence of hypercholesterolemia was higher in women carrying the T allele of rs1746661 than in G/G carriers (72.4% vs. 58.7%, OR=2.010, 95% CI=1.210-3.390), but it was not significantly different in men.
  
  
  CONCLUSIONS
  These results indicate that, although not associated with T2DM, the G allele of rs3480 appears to be associated with increased HbA1c, while the T allele of rs1746661 appears to be associated with higher systolic blood pressure and dyslipidemia in women with T2DM.
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Postgraduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Letícia A
authors.initials: LA
authors.lastname: Brondani
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Boelter
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Postgraduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Taís S
authors.initials: TS
authors.lastname: Assmann
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Postgraduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Cristiane B
authors.initials: CB
authors.lastname: Leitão
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Postgraduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Luís H
authors.initials: LH
authors.lastname: Canani
authors.affiliation: Endocrine Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Postgraduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: dcmoreira@hcpa.edu.br.
authors.forename: Daisy
authors.initials: D
authors.lastname: Crispim
mesh_terms: D000375:Aging; D001794:Blood Pressure / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D005353:Fibronectins / Q000235:genetics* / Q000502:physiology*; D005787:Gene Frequency; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D012727:Sex Characteristics
chemical_list: D002784:Cholesterol; D005353:Fibronectins; D006442:Glycated Hemoglobin; D008055:Lipids; C577593:FNDC5 protein, human
keywords: Blood pressure; Dyslipidemia; FNDC5 gene; Irisin; Type 2 diabetes mellitus