|Associated with slight increase in risks for T2D, breast and prostate cancers.|
|(G;T)||2||1.3x increased type-2 diabetes risk|
|(T;T)||2.2||slight increases (~1.5x) in risk for type-2 diabetes and possibly breast cancer and aggressive prostate cancer|
rs12255372, also known as IVS4G>T and c.483+9017G>T, is a well-studied SNP in the TCF7L2 gene on chromosome 10. In some studies, it has been linked to slight increases in risk for type-2 diabetes, breast cancer and aggressive prostate cancer.
* Type-2 Diabetes Risk Overview: numerous papers report an increase in risk, on the order of 1.5 - 2x for the risk genotypes compared to the non-risk genotype. Key papers include:
- [PMID 16936217] reports the association of rs12255372 and rs7903146 with Type-2 diabetes in a Finnish sample.
- rs12255372 Common variants (rs12255372 and rs7903146) in TCF7L2 seem to be associated with an increased risk of diabetes among persons with impaired glucose tolerance
- [PMID 17671651] Considered for type-2 diabetes with rs7903146 rs12255372 rs10885406.
- [PMID 17971425] Associated in a study of ~1000 Hispanic-Americans with reduced insulin secretion as measured by acute insulin response and adjusted for the degree of insulin sensitivity (p = 0.036).
- [PMID 19033397] This SNP was confirmed to be associated with type-2 diabetes in a study of 500+ Japanese patients plus pooled meta-analysis with 6 previous association studies (also of Japanese).
- A HuGE review and meta-analysis including over 35,000 type-2 diabetes cases and 39,000 controls concluded that the Bayesian odds ratio for rs12255372(T;T) homozygotes and (G;T) heterozygotes versus (G;G) homozygotes was 1.885 (95% credible interval (CrI): 1.698 - 2.088) and 1.360 (95% CrI: 1.291 - 1.433), respectively. Along with 3 other TCF7L2 SNPs, a multiplicative genetic model was indicated.[PMID 19228405]
* Breast Cancer Risk Overview: some papers report a small increase in risk, around 1.1 to 1.2x for the risk genotypes compared to the non-risk genotype, and other papers report no increased risk. Key papers include:
- [PMID 17109766] is the paper which links it to Breast cancer. It suggests the T allele as increasing risk.
- [PMID 26309596] Meta-analysis totaling 4800 breast cancer cases finds a small risk increase (1.07 to 1.17x, depending on genetic model) for T allele
- [PMID 19732438] Mayo Clinic study of 800 patients found no association between rs12255372 and risk for breast cancer or ovarian cancer
- [PMID 23085767] A study of 7,700 Hispanic patients did find increased risk for the rs12255372 T allele, however, it was of borderline statistical significance
* Prostate Cancer Risk Overview:
- [PMID 18302196] In a study of 1,457 prostate cancer cases and 1,351 controls, while there was no association with overall risk, males who were rs12255372(T;T) homozygotes and who had prostate cancer were at elevated relative risk of more aggressive prostate cancer, as defined by high Gleason score (OR = 1.7, CI: 1.0-2.8) or regional/distant stage (OR = 1.7, CI: 1.1-2.6) disease.
Many other papers mention rs12255372, including:
[PMID 18972257] Comparison of genetic risk in three candidate genes (TCF7L2, PPARG, KCNJ11) with traditional risk factors for type 2 diabetes in a population-based study--the HUNT study
[PMID 19183934] TCF7L2 variants are associated with increased proinsulin/insulin ratios but not obesity traits in the Framingham Heart Study
[PMID 19732438] No association between a candidate TCF7L2 variant and risk of breast or ovarian cancer
[PMID 20028944] Gene variants of TCF7L2 influence weight loss and body composition during lifestyle intervention in a risk population for type 2 diabetes
[PMID 20361036] Gene-gene interactions lead to higher risk for development of type 2 diabetes in an ashkenazi jewish population
[PMID 20503258] Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico City
[PMID 20546291] Association of TCF7L2 gene variants with low GAD autoantibody titre in LADA subjects (NIRAD Study 5)
[PMID 21301999] Genetic variations in transcription factor 7-like 2 (TCF7L2) gene: association of TCF7L2 rs12255372(G/T) or rs7903146(C/T) with breast cancer risk and clinico-pathological parameters
[PMID 21109996] Association testing of TCF7L2 polymorphisms with type 2 diabetes in multi-ethnic youth
[PMID 22052079] Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs
[PMID 22402060] Functional analysis of TCF7L2 genetic variants associated with type 2 diabetes
[PMID 22441719] Stronger Association of Common Variants in TCF7L2 Gene with Nonobese Type 2 Diabetes in the Latvian Population
[PMID 17437080] Variants of transcription factor 7-like 2 (TCF7L2) gene predict conversion to type 2 diabetes in the Finnish Diabetes Prevention Study and are associated with impaired glucose regulation and impaired insulin secretion
[PMID 21399856] Variants of transcription factor 7-like 2 (TCF7L2) gene and incident glucose intolerance in Japanese-Brazilians
[PMID 16855264] TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program.
[PMID 16936216] Variant of transcription factor 7-like 2 (TCF7L2) gene and the risk of type 2 diabetes in large cohorts of U.S. women and men.
[PMID 16936218] Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in the Amish: replication and evidence for a role in both insulin secretion and insulin resistance.
[PMID 17003360] Transcription factor TCF7L2 genetic study in the French population: expression in human beta-cells and adipose tissue and strong association with type 2 diabetes.
[PMID 17031610] Association of variants of transcription factor 7-like 2 (TCF7L2) with susceptibility to type 2 diabetes in the Dutch Breda cohort.
[PMID 17093941] Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population.
[PMID 17130514] Polymorphism in the transcription factor 7-like 2 (TCF7L2) gene is associated with reduced insulin secretion in nondiabetic women.
[PMID 17226113] Variants of the transcription factor 7-like 2 gene (TCF7L2) are strongly associated with type 2 diabetes but not with the metabolic syndrome in the MONICA/KORA surveys.
[PMID 17245407] TCF7L2 polymorphisms are associated with type 2 diabetes in northern Sweden.
[PMID 17245589] A genetic variation of the transcription factor 7-like 2 gene is associated with risk of type 2 diabetes in the Japanese population.
[PMID 17259383] Haplotypes of transcription factor 7-like 2 (TCF7L2) gene and its upstream region are associated with type 2 diabetes and age of onset in Mexican Americans.
[PMID 17317761] Transcription factor 7-like 2 (TCF7L2) is associated with gestational diabetes mellitus and interacts with adiposity to alter insulin secretion in Mexican Americans.
[PMID 17340123] Replication study for the association of TCF7L2 with susceptibility to type 2 diabetes in a Japanese population.
[PMID 17429603] TCF7L2 in the Go-DARTS study: evidence for a gene dose effect on both diabetes susceptibility and control of glucose levels.
[PMID 17463248] A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.
[PMID 17470138] Association of TCF7L2 polymorphisms with type 2 diabetes in Mexico City.
[PMID 17503332] Type 2 diabetes TCF7L2 risk genotypes alter birth weight: a study of 24,053 individuals.
[PMID 17579206] Association study of the genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene and type 2 diabetes in the Chinese population.
[PMID 17601994] Variants of the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in an African-American population enriched for nephropathy.
[PMID 17618413] Variants of the TCF7L2 gene are associated with beta cell dysfunction and confer an increased risk of type 2 diabetes mellitus in the ULSAM cohort of Swedish elderly men.
[PMID 17661009] Impaired glucagon-like peptide-1-induced insulin secretion in carriers of transcription factor 7-like 2 (TCF7L2) gene polymorphisms.
[PMID 17665514] Common variants in the TCF7L2 gene and predisposition to type 2 diabetes in UK European Whites, Indian Asians and Afro-Caribbean men and women.
[PMID 17668382] Type 2 diabetes whole-genome association study in four populations: the DiaGen consortium.
[PMID 17697858] The rs12255372(G/T) and rs7903146(C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians.
[PMID 17805508] Disparate genetic influences on polycystic ovary syndrome (PCOS) and type 2 diabetes revealed by a lack of association between common variants within the TCF7L2 gene and PCOS.
[PMID 17903298] Genome-wide association with diabetes-related traits in the Framingham Heart Study.
[PMID 17909099] TCF7L2 is not a major susceptibility gene for type 2 diabetes in Pima Indians: analysis of 3,501 individuals.
[PMID 17934151] A variant of the transcription factor 7-like 2 (TCF7L2) gene and the risk of posttransplantation diabetes mellitus in renal allograft recipients.
[PMID 17972059] TCF7L2 is associated with high serum triacylglycerol and differentially expressed in adipose tissue in families with familial combined hyperlipidaemia.
[PMID 18097733] Association of TCF7L2 polymorphisms with susceptibility to type 2 diabetes in 4,087 Japanese subjects.
[PMID 18248681] Prevalence of common disease-associated variants in Asian Indians.
[PMID 18268068] Variation in TCF7L2 and increased risk of colon cancer: the Atherosclerosis Risk in Communities (ARIC) Study.
[PMID 18282631] Association of TCF7L2 polymorphism with diabetes mellitus, metabolic syndrome, and markers of beta cell function and insulin resistance in a population-based sample of Emirati subjects.
[PMID 18291022] Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population.
[PMID 18437354] TCF7L2 single nucleotide polymorphisms, cardiovascular disease and all-cause mortality: the Atherosclerosis Risk in Communities (ARIC) study.
[PMID 18478343] Association of the TCF7L2 polymorphism with colorectal cancer and adenoma risk.
[PMID 18493736] Exon sequencing and association analysis of polymorphisms in TCF7L2 with type 2 diabetes in a Chinese population.
[PMID 18598350] Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk.
[PMID 18650481] TCF7L2 variants associate with CKD progression and renal function in population-based cohorts.
[PMID 18655717] Weak or no association of TCF7L2 variants with Type 2 diabetes risk in an Arab population.
[PMID 18706099] TCF7L2 gene polymorphisms do not predict susceptibility to diabetes in tropical calcific pancreatitis but may interact with SPINK1 and CTSB mutations in predicting diabetes.
[PMID 18712344] Association of variants of the TCF7L2 gene with increases in the risk of type 2 diabetes and the proinsulin:insulin ratio in the Spanish population.
[PMID 19002430] Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population.
[PMID 19050058] Single nucleotide transcription factor 7-like 2 (TCF7L2) gene polymorphisms in antiislet autoantibody-negative patients at onset of diabetes.
[PMID 19053027] Loci of TCF7L2, HHEX and IDE on chromosome 10q and the susceptibility of their genetic polymorphisms to type 2 diabetes.
[PMID 19141698] Polyunsaturated fatty acids modulate the effect of TCF7L2 gene variants on postprandial lipemia.
[PMID 19211816] TCF7L2, dietary carbohydrate, and risk of type 2 diabetes in US women.
[PMID 19279076] Genetic predisposition, Western dietary pattern, and the risk of type 2 diabetes in men.
[PMID 19309528] Specific and complete human genome amplification with improved yield achieved by phi29 DNA polymerase and a novel primer at elevated temperature.
[PMID 19351735] Evidence for association between polycystic ovary syndrome (PCOS) and TCF7L2 and glucose intolerance in women with PCOS and TCF7L2.
[PMID 19369405] Linkage analysis of albuminuria.
[PMID 19455305] No association of multiple type 2 diabetes loci with type 1 diabetes.
[PMID 19482368] Meta-analysis of the association between SNPs in TCF7L2 and type 2 diabetes in East Asian population.
[PMID 19497595] Genetic variation of FTO and TCF7L2 in premature adrenarche.
[PMID 19602480] Tissue-specific alternative splicing of TCF7L2.
[PMID 19789636] Alternative splicing of TCF7L2 gene in omental and subcutaneous adipose tissue and risk of type 2 diabetes.
[PMID 19825152] TCF7L2 polymorphisms and inflammatory markers before and after treatment with fenofibrate.
[PMID 19924244] TCF7L2 polymorphism rs7903146 is associated with coronary artery disease severity and mortality.
[PMID 20075150] Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study.
[PMID 20144327] A genomics study of type 2 diabetes mellitus in U.S. Air Force personnel.
[PMID 20161033] Personalized pharmacotherapy for Type 2 diabetes mellitus.
[PMID 20648057] Potential role of TCF7L2 gene variants on cardiac sympathetic/parasympathetic activity.
[PMID 21159844] Variants and haplotypes of TCF7L2 are associated with beta-cell function in patients with newly diagnosed type 2 diabetes: the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 1.
[PMID 21278902] Genetic risk profiling for prediction of type 2 diabetes.
[PMID 21349175] TCF7L2 and therapeutic response to sulfonylureas in patients with type 2 diabetes.
[PMID 21423583] Single nucleotide polymorphisms of TCF7L2 are linked to diabetic coronary atherosclerosis.
[PMID 21441683] Screening with OGTT alone or in combination with the Indian diabetes risk score or genotyping of TCF7L2 to detect undiagnosed type 2 diabetes in Asian Indians.
[PMID 21672010] Gestational diabetes mellitus is associated with TCF7L2 gene polymorphisms independent of HLA-DQB1*0602 genotypes and islet cell autoantibodies.
[PMID 21834909] A replication study of the IRS1, CAPN10, TCF7L2, and PPARG gene polymorphisms associated with type 2 diabetes in two different populations of Mexico.
[PMID 21898192] Worldwide distribution of type II diabetes-associated TCF7L2 SNPs: evidence for stratification in Europe.
[PMID 22301903] Association of fibrillin-3 and transcription factor-7-like 2 gene variants with metabolic phenotypes in PCOS.
[PMID 23041303] Association between donor and recipient TCF7L2 gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation in a Han Chinese population
[PMID 23577093] Association of TCF7L2 Gene Polymorphisms with T2DM in the Population of Hyderabad, India
[PMID 23579632] Association of rs12255372 in the TCF7L2 gene with type 2 diabetes mellitus: a meta-analysis
[PMID 23690305] Genetic variants and the risk of gestational diabetes mellitus: a systematic review
[PMID 23188737] TCF7L2 gene polymorphisms and type 2 diabetes risk: a comprehensive and updated meta-analysis involving 121,174 subjects
[PMID 24157263] Polymorphisms of Transcription Factor-7-Like 2 (TCF7L2) gene in Tunisian women with polycystic ovaries syndrome (PCOS)
[PMID 24371822] IRS1, TCF7L2, ADRB1, PPARG, and HHEX Polymorphisms Associated with Atherogenic Risk in Mexican Population
[PMID 22480428] T2D risk haplotypes of the TCF7L2 gene in the Czech population sample: the association with free fatty acids composition.
[PMID 22843023] TCF7L2 gene polymorphisms and type 2 diabetes: association with diabetic retinopathy and cardiovascular autonomic neuropathy.
[PMID 23034957] TCF7L2 genetic variants modulate the effect of dietary fat intake on changes in body composition during a weight-loss intervention.
[PMID 23085767] Associations between TCF7L2 polymorphisms and risk of breast cancer among Hispanic and non-Hispanic white women: the Breast Cancer Health Disparities Study.
[PMID 23107111] Transcription factor-7-like 2 gene variants are strongly associated with type 2 diabetes in Lebanese subjects.
[PMID 23142382] Transcription factor-7-like 2 gene variants are strongly associated with type 2 diabetes in Tunisian Arab subjects.
[PMID 25185411] Association of rs7903146, rs12255372, and rs290487 polymorphisms in TCF7L2 gene with type 2 diabetes in an Iranian Kurdish ethnic group
|Disease||Diabetes mellitus type 2|
|CLNDBN||Diabetes mellitus type 2|
|CLNSRC||OMIM Allelic Variant|
[PMID 25678248] Association between rs7903146 and rs12255372 polymorphisms of transcription factor 7-like 2 gene and polycystic ovary syndrome: a systematic review and meta-analysis
[PMID 26058934] Association of rs12255372 (TCF7L2) and D76N (PDX-1) Polymorphisms with Type 2 Diabetes in a Population Living in Northeast Iran
[PMID 25299103] Association of the rs7903146 and rs12255372 polymorphisms in the TCF7L2 gene with type 2 diabetes in a population from northeastern Brazil
[PMID 26201011] Design of an allele-specific PCR assay to genotype the rs12255372 SNP in a pilot study of association between common TCF7L2 polymorphisms and type 2 diabetes in Venezuelans
[PMID 27605886] TCF7L2 rs7903146 polymorphism is associated with gastric cancer: A case-control study in the Venezuelan population.
[PMID 28101933] Associations of common variants in the SLC16A11, TCF7L2, and ABCA1 genes with pediatric-onset type 2 diabetes and related glycemic traits in families: A case-control and case-parent trio study.
[PMID 28277135] TCF7L2, CAPN10 polymorphisms are associated with gestational diabetes mellitus (GDM) risks: a meta-analysis.
[PMID 28352326] Genetic variants in KCNJ11, TCF7L2 and HNF4A are associated with type 2 diabetes, BMI and dyslipidemia in families of Northeastern Mexico: A pilot study.