Background: Hashimotos thyroiditis (HT) is a common autoimmune disorder of the thyroid (AITD) which affects about 12% of the European population. The disease often clusters in families, which is why many attempts have been undertaken to find the genetic background that would underly the predisposition to HT. In contrast to another AITD - Graves disease, results of genetic analyses have been ambiguous and have failed to find a major genetic locus that would be essential for HT development.
Aim: To assess the joined impact of disease loci associated in the literature with HT predisposition.
Methods: One hundred and forty seven HT fully-symptomatic patients and 147 healthy controls (matched for age, gender, incomes, education, marital status and place of descent), unrelated to each other, were genotyped for 40 polymorphisms (Illumina GoldenGate, custom panel), which were located in genes most often tested in literature for association with AITD, or typed out by genome-wide association studies. All polymorphisms were confirmed to be in Hardy-Weinberg equilibrium in the control group (P>0.05). Variations in the HLA-DRB1 gene were analyzed by Sanger sequencing. A genetic model for HT predisposition was obtained with use of stepwise logistic regression. Biostatistical analyses were performed with the programs Statistica v12, Plink v1.9, and GCTA v1.02.
Results: The model which best explained the predisposition to HT contained seven polymorphisms in the genes PTPN22, IFIH1, CTLA4, RGS6, TNMD, NOX1, and the promoter region of FAM155A. The model was able to classify correctly 67% of all cases, similarly for both groups. Such a model explained only 5.12% of the between-group variance. This value is in agreement with a model published lately for another autoimmune disorder.
Discussion: Our data confirm that there seem to be no genes that are per se crucial for HT development. Future analyses on HT predisposition should focus on the joined influence of many polymorphisms in different genetic regions.
20 - 23 May 2017
European Society of Endocrinology