Endocrine Abstracts

Identified genetic players for most common diseases are not sufficient to explain their heritability. This situation is known as the missing heritability problem. One among the possible explanations is the impact of rare variants. We present our own results of rare variants in the gene SLC26A4 in Hashimoto’s thyroiditis (HT), which were not found in controls, and therefore confirm the possibility of their impact on this disease. We genotyped 147 Hashimoto’s thyroiditis cases (10.2% men) and 147 controls (13.6% men) matched for age, gender, marital status, education, monthly income, and size of the city they live in. The gene SLC26A4 encoding for a iodine transporter was Sanger-sequenced in 20 HT cases, in order to identify new rare variants in this gene. We identified 2 new variants, which have not been previously reported. Two among the investigated SNPs were not differentially represented in both groups: c.-103T>C, previously associated with Pendred syndrome, and c.1708-18T>A, previously proven as benign. In contrast, variants located in the coding region, which have previously been assigned as benign or likely benign. Those included p.Ser190Arg (n=4 cases), p.Ile300Leu (n=3), p.Phe354Ser (n=3), p.Ala456Ala (n=2), p.Leu597Ser (n=4), p.Val609Gly (n=2) and p.Asp772Tyr (n=1). It seems very probable that rare variants are at least one of the reasons for missing heritability. It seems possible that the variants we identified in HT may play a joint role in HT, as most of them co-occurred in the same patients. Future studies should target genome-wide rare variants, as probably different genes will have a combined role in the risk of those diseases.