Association of Polymorphisms in Toll-Like Receptors 4 and 9 with Autoimmune Thyroid Disease in Korean Pediatric Patients

Abstract

Background: Toll-like receptors (TLRs) have been suggested to be associated with the development of AITD.

Methods: Fifteen single-nucleotide polymorphisms in 7 TLR genes were analyzed in 104 Korean children (girls = 86, boys = 18) with AITD (Hashimoto disease (HD) = 44, Graves' disease (GD) = 60, thyroid-associated ophthalmopathy (TAO) = 29, and non-TAO = 31) with 183 controls.

Results: GD showed higher frequencies of the TLR4 rs1927911 C allele than control. TAO showed a lower frequency of the TLR4 rs1927911 CT genotype and non-TAO showed a higher frequency of the TLR4 rs1927911 CC genotype than control. The frequency of the TLR9 rs187084 CC genotype in TAO was higher than that in non-TAO. GD females showed a higher frequency of the TLR4 rs10759932 T allele, rs1927911 CC genotype, and the rs1927911 C allele than controls. GD males showed a higher frequency of the TLR4 rs10759932 CC genotype and rs1927911 TT genotype and lower frequency of the rs1927911 CT genotype than control. The frequency of the TLR4 rs10759932 CC genotype, C allele and rs1927911 TT genotype, and T allele in a GD female were lower than in a GD male.

Conclusions: Our results suggest that TLR4 and 9 polymorphisms might contribute to the pathogenesis of GD and TAO.

Figure 1

Analysis of TLR4 gene polymorphism between female and male in Graves' disease (GD); the frequency of the TLR4 rs10759932 CC genotype (OR = 24; 95% CI, 2.52–228.3, P = 0.002, Pc = 0.006), C allele (OR = 3.29; 95% CI, 1.26–8.63, P = 0.012, Pc = 0.025), and TLR4 rs1927911 TT genotype (OR = 9.17; 95% CI, 1.82–46.20, P = 0.008, Pc = 0.024); and T allele (OR = 2.5; 95% CI, 1.02–6.15, P = 0.042) in GD female was lower than that in GD male.