Endocrine Abstracts

Background: Graves’ Disease (GD) is one of the most common organ specific autoimmune disorders, being characterized by an abnormal production of stimulating autoantibodies to the thyrotropin receptor (TSHR). Some studies demonstrated that genetic polymorphisms in certain cytokines, namely interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), are associated with a greater susceptibility of developing GD. Our aim was to evaluate if these single nucleotide polymorphisms (SNP) also contribute to metabolic disturbances in GD patients.

Methods: Glycemic and lipid profiles were assessed in a case-control study comprising 97 Graves’ disease patients. Genetic variants in IL6-174 G/C (rs1800795), TNFA-308 G/A (rs1800629), IL1B-511 C/T (rs16944), and IFNGR1-56 T/C (rs2234711) were discriminated by real-time PCR using TaqMan SNP genotyping assays. To evaluate the associations of SNP genotypes with glycemic and lipid profiles we used independent t test and Kruskal-Wallis test. We also performed linear and logistic regression models adjusted for age and sex.

Results: Within our sample of 97 patients with GD, 91.8% (89 subjects) were females, with a mean age of 44.4 ± 15.1 years. The mean TSH level of our population was 0.4 (0.0-1.3) μUI/l, while the mean levels of FT3 and FT4 were 3.0 (2.6-3.5) ng/ml and 1.1 (0.9-1.4) μg/ml, respectively. The allele T in IL1B-511 C/T was significantly associated with a higher prevalence of diabetes (P=0.029). The A allele in TNFA-308 G/A was associated with significant lower levels of HDL cholesterol (P=0.037), and with higher levels of fasting insulin (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 in the adjusted analysis (P=0.047), as well as higher levels of C peptide (P=0.026). In addition, the analysis of the insulin-resistance indexes showed that HOMA-IR was significantly higher in the T allele group (P=0.035), while the QUICKI’s mean was lower when the T allele was present (P=0.035).

Conclusions: Our study demonstrated that SNP in some pro-inflammatory cytokines may affect lipid and glycemic profiles in GD patients. TNF-α-308 A allele might be responsible for lower levels of HDL cholesterol along with increased beta cell function in patients with GD. IL1β-511 T allele may be linked with a higher prevalence of diabetes among GD patients, and IFNGR1-56 T allele is associated with insulin resistance. More studies are needed to evaluate the clinical relevance of these findings.