IL‐12B and IL‐10 gene polymorphisms in the development of Hashimoto's thyroiditis

Abstract

Functional genetic polymorphisms that altered gene expression of cytokines are candidate genetic factors that could modulate the development and progression of Hashimoto's thyroiditis (HT). IL-12B gene encoded the IL-12p40 subunit, which is included in the pro-inflammatory heterodimeric cytokines IL-12p70 and IL-23. IL-10 is an important Treg cytokine suppressing inflammatory cytokine production and autoimmunity. This study was designed to compare -1082A/GIL-10 and +1188A/C3'UTRIL-12B genotype distribution in 130 patients with HT to a group of 157 healthy controls in attempts to determine an association with HT development. Genotyping for the 3'UTRA/C IL-12B polymorphism was performed using RFLP-PCR and genotyping for -1082A/G IL-10 by ARMS-PCR assay. Patients with HT were divided into euthyroid and hypothyroid stages. There were no significant differences in the genotype and allele frequencies of the IL-12B polymorphism between patients with HT and controls. We observed higher euthyroid HT risk for individuals with CC genotype, unlike to develop hypothyroidism with OR=1.68. Regarding the polymorphism rs1800896, it was shown the significantly higher frequency of homozygous genotype GG in cases vs controls (OR=2.19; P=0.024). Moreover, the combination of genotype AA of 3'UTRIL-12B with GG of -1082IL-10 was associated with a threefold increasing risk (OR=3.188; P=0.022) of developing HT compared to individuals with the presence of 3'UTR allele C (AC+CC) simultaneously with AA genotype of -1082IL-10. Our data raise the possibility that the combined effect of polymorphisms from proinflammatory and anti-inflammatory cytokines may be more decisive to HT development.