Polymorphisms in pro inflammatory cytokines' genes and metabolic changes in patients with Graves disease

Abstract

Background: Graves' Disease (GD) is one of the most common organ specific autoimmune disorders. Some single nucleotide polymorphism (SNP) in pro-inflammatory cytokines have already been linked to an increased susceptibility of developing GD. Aim: to evaluate if these SNP also contribute to metabolic disturbances in GD patients, resulting in alterations in their lipid and glycemic profile. Methods: Glycemic and lipid profiles were assessed in a case-control study comprising 98 Graves' disease patients from Portugal. Genetic variants in IL6-174 G/C (rs1800795), TNFα-308 G/A (rs1800629), IL1β-511 C/T (rs16944), and IFNGR1-56 T/C (rs2234711) were discriminated by real-time PCR using TaqMan SNP genotyping assays. The associations of genetic variants with lipid and glycemic profile were evaluated with analysis unadjusted and adjusted for age and sex. Results: The allele T in IL1 β -511 C/T was significantly associated with a higher prevalence of diabetes (p = 0.029). The A allele in TNFα-308 G/A was associated with significant lower levels of HDL cholesterol only in the unadjusted analysis (p=0.037), and with higher levels of fasting insulin in the adjusted analysis (p= 0.042) along with HOMA-β higher levels in both analyses (p= 0.027; p= 0.020). The T allele in IFNGR1-56 T/C polymorphism was associated with significantly higher mean values of fasting glucose only in the adjusted analysis (p=0.047), as well as higher levels of C peptide in the unadjusted analysis (p=0.026). Conclusions: This study reports significant associations of genetic variants in TNFα with lipid profile, as well as polymorphisms in IL1β and IFNGR1 with glycemic profile.