Mechanisms of autoimmune thyroid diseases: from genetics to epigenetics.
Recent advances in our understanding of genetic-epigenetic interactions have unraveled new mechanisms underlying the etiology of complex autoimmune diseases. Autoimmune thyroid diseases (AITDs) are highly prevalent, affecting 1% to 5% of the population. The major AITDs include Graves disease (GD) and Hashimoto's thyroiditis (HT); although these diseases contrast clinically, their pathogenesis involves shared immunogenetic mechanisms. Genetic data point to the involvement of both shared and unique genes. Among the shared susceptibility genes, HLA-DRβ1-Arg74 (human leukocyte antigen DR containing an arginine at position β74) confers the strongest risk. Recent genome-wide analyses have revealed new putative candidate genes. Epigenetic modulation is emerging as a major mechanism by which environmental factors interact with AITD susceptibility genes. Dissecting the genetic-epigenetic interactions underlying the pathogenesis of AITD is essential to uncover new therapeutic targets.
Division of Endocrinology, Department of Medicine, Mount Sinai Medical Center, New York, NY 10029; email: yaron.tomer@mssm.edu.
Yaron
Y
Tomer
D001327:Autoimmune Diseases / Q000235:genetics*; D044127:Epigenesis, Genetic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D013959:Thyroid Diseases / Q000235:genetics*