The rs1746661 and rs3480 polymorphisms in the FNDC5 (Irisin) gene are associated with increased systolic blood pressure in white patients with type 2 diabetes mellitus

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 796-817-Diabetes Genetics & Epidemiology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-809
Letícia de Almeida Brondani*1, Tais Silveira Assmann1, Gabriela Boelter2, Luis Henrique Canani3 and Daisy Crispim4
1Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil, 2Hospital de Clínicas de Porto Alegre, 3Hosp de Clinicas - Porto Alegre, Porto Alegre, Brazil, 4Clinical Hospital from Porto Alegre, Porto Alegre, 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 can 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 747 patients with T2DM and 351 non-diabetic 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 and allele frequencies of the rs1746661 and rs3480 polymorphisms did not differ significantly between non-diabetic subjects and patients with T2DM (P>0.05). Both polymorphisms are in partial linkage disequilibrium (|D’|=0.88; r²=0.235). The haplotype frequencies also did not differ among non-diabetic and T2DM samples (P=0.913). Interestingly, T2DM patients carrying the G allele of the rs3480 polymorphism had higher levels of systolic blood pressure (SBP) than patients with the A/A genotype (142.6 ± 23.8 vs. 138.8 ± 21.5 mm/Hg; P=0.041), adjusting for covariates. In the same way, T2DM patients carrying the T allele of the rs1746661 polymorphism showed increased SBP as compared to patients with the G/G genotype (146.0 ± 21.4 vs. 141.2 ± 22.7 mm/Hg; P=0.003), adjusting for covariates. Furthermore, T2DM patients carrying the rs1746661 T allele had increased levels of total cholesterol (T/T-G/T = 217.1 ± 48.5 vs. G/G = 206.0 ± 48.1 mg/dL; P=0.024) and LDL cholesterol (T/T-G/T = 135.4 ± 43.4 vs. G/G = 126.8 ± 46.9 mg/dL; P=0.018) after adjustment for covariates.

Conclusion: This study showed no association between the rs1746661 and rs3480 polymorphisms and T2DM; however, both polymorphisms seem to be associated with increased SBP in T2DM patients. The rs1746661 polymorphism also is associated with increased levels of total cholesterol and LDL cholesterol.

Nothing to Disclose: LDAB, TSA, GB, LHC, DC

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Sources of Research Support: Financial support: CAPES, CNPq, FIPE-HCPA.