rs180223

A 2015 research study titled "Correlation between thyroglobulin gene polymorphisms and autoimmune thyroid disease" focused on the Han Chinese population. A total of 270 patients with AITD and 135 healthy controls were enrolled. They found "The Tg SNP frequency distribution was significantly different between Han populations of the Northern regions of Henan province and the Xi'an regions of Shaanxi province" (Abstract). *Separate ODs were found for the following TG gene SNPs: **E10SNP24 T/G rs180223 = TT 1.35, TG 11.50, GG 0.14, (TG OD was 95%CI = 4.89-27.06, p=<0.01) **E10SNP158 T/C rs2069550 = TT 1.07, TC 0.96, CC 1.03 **E12SNP A/G rs853326 = AA 0.51, AG 0.23, GG 4.22 (GG OD was 95%CI = 2.65-6.73, p=<0.01) **E33SNP C/T rs2076740 = CC 1.11, CT 0.93, TT 0.98. *More significant combined ODs were received when these SNPs were were combined: **GTAC = 0.22 Hypothyroidism (HY), 0.22 Graves(GD), 0.24 Hashimoto's (HT) **GCGC = 0.57 HT **GTGC = 3.57 GD, 3.50 HT **TTGC = 4.00 HY **TCGC = 5.23 HY, 3.00 GD, 4.45 HT This 2003 article titled "Amino acid substitutions in the thyroglobulin gene are associated with susceptibility to human and murine autoimmune thyroid disease" performed case control association studies for 14 TG SNPs in 285 Caucasian AITD patients and 150 Caucasian controls. They found that within the TG gene, "exon 10-12 SNP cluster and an exon 33 SNP were significantly associated with AITD." *Four polymorphisms, considered separately, had ODs over 1.3, but p values were not strong, between 0.003 and 0.12. (Supplementary tables 10,11,12) *However, they discovered more significant ODs and p values when combining one or more exon 10-12 SNP alleles with the CC homozygous exon 33 polymorphism: ** with or without E10SNP24 T/G = rs180223 = T allele, ** with or without E10SNP158 T/C = rs2069550 = T allele, ** with or without E12SNP A/G = rs853326 = A allele, ** always with E33SNP = rs2076740 = CC polymorphism *ODs for risk of AITD, GD and HT were given with the above risk alleles in combination (Table 2): **T,T,A,CC = 2.49 (p=0.0004); **T,--,--,CC = 2.42 (p=0.0005); **--,T,--,CC = 2.52 (p=0.0003); **--,--,A,CC = 2.43 (p=0.0004) *The ODs for risk of HT and GD were similar, all above 2.38 with p values equally or more significant. (Tables 3,4) *Adding significance for the exon 33 SNP in particular, they discovered "an interaction between HLA-DR3 and the exon 33 SNP, giving an odds ratio of 6.1 for Graves' disease." However, one must keep in mind the small sample size of this study. In addition, this study focused on a Caucasian sample, while some other studies have focused on Chinese samples.

G;G

see text at rs180223

G;T

The 1.3x risk was for carriers of the minor allele in a Caucasian population. The 11.5x risk was for heterozygotes (GT only) in the Han Chinese population in a 2015 study. See text at rs180223

T;T

Only the GG variant is protective. See text at rs180223