Systemic arterial hypertension in patients with type 1 diabetes mellitus is associated with the A allele of the rs1990760 (G/A) polymorphism in the IFIH1 gene and with expression of this gene in mononuclear cells

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

Poster Board MON-811
Ana Paula Bouças*1, Letícia de Almeida Brondani2, Fernanda Santos de Oliveira1, Natalia Emerim Lemos3, Luis Henrique Canani4 and Daisy Crispim5
1Hospital de Clinicas de Porto Alegre, 2Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil, 3Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil, 4Hosp de Clinicas - Porto Alegre, Porto Alegre, Brazil, 5Clinical Hospital from Porto Alegre, Porto Alegre, Brazil
Introduction: Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by the interplay of both environmental and genetic factors. Several studies indicate that viruses have an important role in triggering the autoimmune destruction of pancreatic beta-cells. IFIH1/MDA5 gene belongs to a family of pattern-recognition receptors that mediates induction of interferon response to viral RNA, and is a candidate for T1DM because it encodes a cytoplasmic receptor that play a major role in the recognition of viral nucleic acids and, consequently, in the immune response against viruses. In this context, IFIH1 protein may stimulate autoreactive T cells leading to T1DM.  Indeed, the IFIH1 rs1990760 (G/A) polymorphism has been associated with T1DM in some populations.

Objectives: To evaluate the association between the rs1990760 (G/A) polymorphism and T1DM or its clinical characteristics in a Southeast Brazilian population, and to analyze the IFIH1 gene expression in mononuclear cells from T1DM patients according to different genotypes of this polymorphism.

Methods: We analyzed 527 patients with T1DM and 517 nondiabetic subjects. The polymorphism was genotyped by Real-Time (RT) PCR using TaqMan MGB probes. IFIH1 gene expression in 26 samples of mononuclear cells was evaluated using RT-qPCR.

Results: Genotype frequencies of the rs1990760 polymorphism did not differ between T1DM patients and nondiabetic subjects (P=0.139) Moreover, the A allele frequency was similar between T1DM and nondiabetic samples (0.53 vs. 0.50; P=0.129). In T1DM patients, glycemic and lipid profile, body mass index, and age of T1DM onset did not differ significantly among different genotypes of this polymorphism. However, A allele carriers showed lower levels of both systolic (128.5 ± 18.9 vs. 119.7 ± 18.2 mm/Hg, P=0.019) and diastolic (82.4 ± 13.5 vs. 76.6 ± 10.6 mm/Hg, P=0.004) blood pressures as compared to G/G genotype patients, adjusting for covariates. The frequency of arterial hypertension (AH) was also increased in A allele carriers with T1DM, adjusting for covariates (P=0.019). IFIH1 gene expression in mononuclear cells did not differ among the three genotypes of the rs1990760 polymorphism. Interestingly, IFIH1 gene expression was higher in mononuclear cells from T1DM patients with AH as compared with T1DM patients without AH [median 6.7 (range 1.7-41.2) vs. 1.8 (1.3-73.3), respectively; P=0.036].

Conclusions: The present study showed no association between the rs1990760 polymorphism and T1DM; however, the A allele was associated with protection to AH in T1DM patients as well as with an increase IFIH1 gene expression.

Nothing to Disclose: APB, LDAB, FSD, NEL, LHC, DC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: CNPq, FAPERGS, FIPE-HCPA.