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rs2076740

From SNPedia

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Geno Mag Summary
(C;C) 2 2.4-6.1 risk of Autoimmune thyroid disease, if other SNP risk alleles present
(C;T) 1.5 1.56x risk of autoimmune thyroid disease
(T;T) 1 no increased risk of autoimmune thyroid disease
ReferenceGRCh38 38.1/141
Chromosome8
Position132971813
GeneTG
is asnp
is mentioned by
dbSNPrs2076740
dbSNP (old)rs2076740
ClinGenrs2076740
ebirs2076740
HLIrs2076740
Exacrs2076740
Varsomers2076740
Maprs2076740
PheGenIrs2076740
Biobankrs2076740
1000 genomesrs2076740
hgdprs2076740
ensemblrs2076740
gopubmedrs2076740
geneviewrs2076740
scholarrs2076740
googlers2076740
pharmgkbrs2076740
gwascentralrs2076740
openSNPrs2076740
23andMers2076740
23andMe allrs2076740
SNP Nexus

SNPshotrs2076740
SNPdbers2076740
MSV3drs2076740
GWAS Ctlgrs2076740
Merged fromRs11535853
GMAF0.3301
Max Magnitude2
? (C;C) (C;T) (T;T) 28
OMIM188450
Desc
Variant0008
Relatedalso
[PMID 14657345OA-icon.png] 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 26099577OA-icon.png] 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 26963610OA-icon.png] 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


ClinVar
Risk Rs2076740(T;T)
Alt Rs2076740(T;T)
Reference Rs2076740(C;C)
Significance Other
Disease Autoimmune thyroid disease 3 not specified Thyroid dyshormonogenesis
Variation info
Gene TG
CLNDBN Autoimmune thyroid disease 3 not specified Thyroid dyshormonogenesis
Reversed 0
HGVS NC_000008.10:g.133984058C>T
CLNSRC OMIM Allelic Variant UniProtKB (protein)
CLNACC RCV000013533.3, RCV000251808.1, RCV000277644.1,


GET Evidence
TG-R1999W
aa_change Arg1999Trp
aa_change_short R1999W
impact not reviewed
qualified_impact Insufficiently evaluated not reviewed
overall_frequency 0.394776
summary