ESPE Abstracts (2016) 86 P-P1-894

Comprehensive Analysis of Seven Toll-Like Receptor Genes Including 15 Single-Nucleotide Polymorphisms with Autoimmune Thyroid Disease in Korean Children

Won Kyoung Choa, Jung-Pil Jangb, Moon Bae Ahna, Min Ho Junga, Tai-Gyu Kimb,c, Byung-Kyu Suha, Shin Hee Kima, Kyoung Soon Choa & So Hyun Parka


aDepartment of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; bDepartment of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; cHematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea


Background: The Toll-like receptors (TLRs) are germline-encoded receptors that play an essential role in initiating the immune response against pathogens.

Objective and hypotheses: In this study, we assess the association of TLR polymorphism with autoimmune thyroid disease (AITD) in Korean children.

Method: Seven Toll-like receptor genes (TLR-1, -2, -3, -4, -5, -6, -9) including 15 single-nucleotide polymorphisms were analyzed on 104 Korean children with AITD [Hashimoto′s disease (HD)=40, Graves′ disease (GD)=60 (thyroid-associated ophthalmopathy (TAO)=29, non-TAO=31)] and 192 healthy individuals.

Results: In total AITD, the frequencies of these alleles had no statistical difference with controls. In HD, the frequencies of the TLR3 rs3775296 AA genotype (OR=3.45, P<0.022) was higher, whereas the TLR3 rs3775296 C allele (OR=0.29, cP<0.044) showed lower frequencies than in the healthy controls. In GD, the frequencies of the TLR4 rs1927911 CC genotype (OR=2.18, cP<0.027) was higher, whereas the TLR4 rs1927911 CT genotype (OR=0.48, P<0.018) and TLR4 rs1927911 T allele (OR=0.46, cP<0.018) showed lower frequencies than in the healthy controls. Between HD and GD, the frequencies of the TLR4 rs1927911 CC genotype in HD (OR=0.37, cP<0.048) was lower, whereas TLR4 rs1927911 CT genotype in HD (OR=2.63, P<0.017) and TLR4 rs1927911 T allele in HD (OR=2.72, cP<0.032) showed higher frequencies than GD. In TAO, the frequencies of the TLR4 rs1927911 CC genotype (OR=2.31, P<0.029) was higher, whereas TLR4 rs1927911 T allele (OR=0.43, P<0.029) showed lower frequencies than in the healthy controls. Between TAO and non-TAO, the frequencies of the TLR9 rs 187084 CC genotype in non-TAO (OR=5.52, P<0.028) was higher, whereas TLR9 rs 187084 T allele in non-TAO (OR=0.18, P<0.028) was lower than TAO.

Conclusion: Our results suggest that TLR-3,-4 and -9 gene polymorphisms may contribute to the pathogenesis of AITD and TAO.