The combination of a lack of impact of the TCF7L2 genotypes on the ability to lose weight, but the presence of a consistent effect on the proinsulin:insulin ratio over the course of DPP, suggests that high-risk genotype carriers at this locus can successfully lose weight to counter diabetes risk despite persistent deficits in insulin production.
Human genetic studies have revealed that the T minor allele of single nucleotide polymorphism rs7903146 in the transcription factor 7-like 2 (TCF7L2) gene is strongly associated with an increased risk of diabetes by 30%-40%.
Single nucleotide polymorphisms (SNPs) in the transcription factor 7-like 2 gene (TCF7L2) represent the strongest and most reproducible genetic associations with diabetes.
Our data indicate for the first time that TCF7L2 gene variants confer an increased risk for early impairment of glucose metabolism in obese children, which is consistent with adult studies identifying TCF7L2 as a major diabetes susceptibility gene.
The results indicated that the TCF7L2rs11196172 polymorphism increases the risk of CRC independently, with no evidence of an interaction with diabetes or obesity.
Analysis of TCF7L2rs7903146 in normal controls and diabetics with or without nephropathy demonstrated that the 'T' allele is associated with both diabetes (p = 0.049) and DN (p = 0.024), but this association is not independent of T2DM.
The transcription factor TCF7L2 is particularly strongly associated with risk for diabetes and appears to be fundamentally important in both canonical Wnt signaling and beta-cell functioning.
The aim of the study was to explore the correlation between rs7903146 and rs290487 polymorphisms in transcription factor 7-like 2 (TCF7L2) gene and diabetic nephropathy (DN) in Chinese Han population.Polymerase chain reaction-restriction fragment length polymorphism was used to determine genotypes of TCF7L2 polymorphisms in 90 patients with DN and 96 diabetes patients without DN.
Transcription factor 7-like 2 (TCF7L2), which previously known as TCF-4, is a major form of transcription factor involved in the downstream WNT signaling and exhibits the strongest association to diabetes susceptibility.
Recent human studies suggest transcription factor 7-like 2 (TCF7L2) polymorphism predisposes to diabetes through modulation of beta-cell function and modulates lipid levels in familial dyslipidemia.
Maternal GCK and TCF7L2 variants are associated with glucose levels known to carry an increased risk of adverse pregnancy outcome in women without overt diabetes.
The TCF7L2 was associated with susceptibility for gestational diabetes independently of the presence of HLA-DQB1*0602 and islet cell autoantibodies and other factors such as maternal age, number of pregnancies, family history of diabetes and other HLA-DQ genotypes.
TCF7L2rs7903146 C>T polymorphism is associated with diabetes in the general population but its independent impact on cardiovascular disease is debated.
In contrast, variants near insulin-like growth factor-binding protein 2 (IGFBP2), CDK5 regulatory subunit associated protein 1-like 1 (CDKAL1), solute carreir family 30 (zinc transporter), member 8 (SLC30A8), hematopoietically-expressed homeobox (HHEX), and transcription factor 7-like2 (TCF7L2) were clearly associated with diabetes; no evidence for an association to CAC was observable.
In addition, the TCF7L2rs290487 TT genotype was associated with abdominal obesity and the GCG rs12104705 CC genotype was associated with both general obesity and abdominal obesity in case of new-onset diabetes.
After adjusting for known confounding factors, we found a significant association between TCF7L2/rs122555372 and C-peptide (β = -0.76, P = .005) in patients with diabetes and between fasting glucose (β = 2.05, P = .039) and homeostatic model assessment of β-cell function (β = -32.14, P = .025) levels in individuals without diabetes.
The frequency of diabetes-associated TCF7L2 genotypes was greater in cases ascertained for positive family history and early onset (rs4606565, P = 0.02); the population-attributable risk, estimated from the least-selected cases, is approximately 16%.
In subjects without known diabetes (n=961) recruited from the Chennai Urban Rural Epidemiology Study (CURES), OGTT, IDRS, and genotyping of rs12255372 (G/T) and rs7903146(C/T) of TCF7L2 polymorphisms were done.