Abstract
BackgroundThe rs1990760 polymorphism of interferon induced with helicase C domain 1 (IFIH1) has been associated with type 1 diabetes mellitus (T1DM). Here, we investigated whether this polymorphism is associated with T1DM or its clinical characteristics in a Brazilian population, and if IFIH1 gene expression in mononuclear cells from T1DM patients differs according to the genotypes of this polymorphism. A meta-analysis was also conducted to evaluate if the rs1990760 polymorphism is associated with T1DM.MethodsFrequencies of the rs1990760 polymorphism were analyzed in 527 T1DM patients and in 517 healthy subjects. IFIH1 gene expressions according to genotypes were measured in a sub-sample of 26 T1DM patients by quantitative real-time PCR.ResultsOur data show the association of the A allele with risk to T1DM under a dominant model of inheritance [odds ratio (OR) = 1.421, P = 0.037], adjusting for ethnicity. The meta-analysis revealed significant association between the rs199760A allele and risk for T1DM for all analyzed inheritance models. Surprisingly, T1DM patients carrying the A allele showed lower levels of systolic (P = 0.001) and diastolic (P = 1×10−10) blood pressures as compared to G/G carriers. Furthermore, the A/A genotype seems to be associated with protection to arterial hypertension (AH) after adjustment for covariates (OR = 0.339, P = 0.019). IFIH1 gene expression in mononuclear cells from 26 T1DM patients did not differ among genotypes (P = 0.274). Nevertheless, IFIH1 gene expression was increased in mononuclear cells from T1DM patients with AH as compared with T1DM patients without AH [6.7 (1.7–2.0) vs. 1.8 (1.3–7.1) arbitrary units; P = 0.036]. The association with blood pressures and AH was not observed in patients with type 2 diabetes mellitus.ConclusionsOur results indicate that the rs1990760 polymorphism is associated with T1DM. Interestingly, the rs1990760 A allele seems to be associated with protection for AH in T1DM patients. Further studies are needed to confirm the association with AH.
Highlights
Type 1 diabetes mellitus (T1DM), which accounts for 5–10% of those with diabetes, results from a cellular-mediated autoimmune destruction of the pancreatic beta-cells, which renders patients insulin-dependent for life [1]
Studies were excluded from the analysis if the genotype distributions in control group deviated from those predicted by the Hardy–Weinberg equilibrium (HWE) or if they did not have sufficient data to estimate an odds ratio (OR) with 95% CI
Males comprised 48.0% of the sample, 16.1% were black, 28% of all patients had arterial hypertension (AH), 45.1% had some degree of diabetic retinopathy (DR), and 35.2% had some degree of diabetic nephropathy (DN)
Summary
Type 1 diabetes mellitus (T1DM), which accounts for 5–10% of those with diabetes, results from a cellular-mediated autoimmune destruction of the pancreatic beta-cells, which renders patients insulin-dependent for life [1]. Other non-HLA loci have smaller effects on disease risk compared to HLA, and include the insulin gene, the CTLA4 gene, the PTPN22 gene, the IL2RA gene, and the interferon induced with helicase C domain 1 (IFIH1) gene [4]. The rs1990760 polymorphism of interferon induced with helicase C domain 1 (IFIH1) has been associated with type 1 diabetes mellitus (T1DM). We investigated whether this polymorphism is associated with T1DM or its clinical characteristics in a Brazilian population, and if IFIH1 gene expression in mononuclear cells from T1DM patients differs according to the genotypes of this polymorphism. A meta-analysis was conducted to evaluate if the rs1990760 polymorphism is associated with T1DM
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