Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2014) 35 P359 | DOI: 10.1530/endoabs.35.P359

ECE2014 Poster Presentations Diabetes (epidemiology, pathophysiology) (63 abstracts)

The rs1746661 polymorphism in the FNDC5 (Irisin) gene is associated with increased levels of total cholesterol in white patients with type 2 diabetes mellitus

Ana Paula Bouças 1, , Leticia Brondani 1, , Tais Assman 1, , Gabriela Boelter 1 , Luis Henrique Canani 1, & Daisy Crispim 1,

1Hospital de Clinicas, Porto Alegre, Rio Grande do Sul, Brazil; 2Universidade Federal do Rio Grande do Sul:Postgraduate Program in Medical Sciences, Endocrinology, Porto Alegre, Rio Grande do Sul, Brazil.

Introduction: Type 2 diabetes mellitus (T2DM) is a highly prevalent chronic metabolic disease with strong co-morbidity with obesity and cardiovascular diseases. FNDC5 gene encodes a type I membrane protein that is processed proteolytically to form a newly identified hormone secreted into the blood, termed irisin. After induction by exercise, irisin activates profound changes in the subcutaneous adipose tissue, stimulating browning and UCP1 gene expression. This causes a significant increase in total body energy expenditure and resistance to obesity-linked insulin resistance. Thus, polymorphisms in the FNDC5 gene might be associated with T2DM and related disorders.

Objective: To evaluate the association of the FNDC5 rs3480 (G/A) and rs1746661 (G/T) polymorphisms, individually or in combination, with T2DM or its clinical features.

Methods: We analyzed 1,006 T2DM patients and 431 nondiabetic subjects. Polymorphisms were genotyped by RT-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 and allele frequencies of the rs1746661 and rs3480 polymorphisms did not differ significantly between nondiabetic subjects and T2DM patients (P>0.05). Both polymorphisms are in partial linkage disequilibrium (|D’|=0.88; r2=0.235). Haplotype frequencies also did not differ among nondiabetic and T2DM groups (P=0.913). T2DM patients carrying the rs1746661 T allele had increased levels of total cholesterol when compared with the G/G genotype (T/T-G/T: 212.4±47.6 G/G: 203.8±47.2 mg/dl; P=0.023) after adjustment for covariates. Furthermore, patients carrying the mutated haplotype in homozygosis had increased levels of total cholesterol (P=0.014) as well as increased risk of hypercholesterolemia (OR=1.49 (1.01–2.19); P=0.046), after adjustment for covariables.

Conclusion: This study showed no association between the rs1746661 and rs3480 polymorphisms and T2DM; however, the rs1746661 polymorphism was associated with increased levels of total cholesterol.

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