|| 2.4-6.1 risk of Autoimmune thyroid disease, if other SNP risk alleles present
|| 1.56x risk of autoimmune thyroid disease
|| no increased risk of autoimmune thyroid disease
|?|| (C;C) (C;T) (T;T) ||28|
] 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 (autoimmune thyroid disease) 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 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 (Hashimoto's thyroiditis) and GD (Graves' disease) 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" resulting in an odds ratio of 6.1 for GD.
NOTE: The large odds ratio may be due to the small sample size of this study. In addition, this study focused on a Caucasian sample. Nevertheless, other studies focused on regional samples have shown similar trends.
[PMID 26099577] 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
[PMID 26963610] A 2016 study titled "Association of Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Thyroglobulin (TG) Genetic Variants with Autoimmune Hypothyroidism" sampled 84 hypothyroidism patients and 62 controls from Gujarat, India. Researchers found that polymorphisms of the TG gene's exon 33 SNP rs2076740 significantly increased the odds of autoimmune hypothyroidism: Odds ratios were
- for TT, 1.0 (Genotypes were similar between patients and controls)
- for TC, 7.519 (95%CI 2.329 to 24.27, p=0.0003) compared to AA (7.729 after adjustment for age and gender).
- for CC, 20.54 (95%CI 5.065 to 83.30, p=0.0001) compared to AA (15.151 after adjustment for age and gender).
Researchers theorized that the TG polymorphism may "change its antigenicity making it more immunogenic" (Conclusion). They also found significant differences in patients vs. controls when analyzing the CTLA4 SNP Exon1 (+49A/G) rs231775. NOTE: The large odds ratio may be attributed to the small number of patients and controls and/or the regional sample.
[PMID 22265031] Epistasis between the HSD17B4 and TG polymorphisms is associated with premature ovarian failure