This Perspectives in Care article highlights the role of type 2 diabetes-associated genetic factors (e.g., gene variants at transcription factor 7-like 2 [<i>TCF7L2</i>]) and obesity (via insulin resistance, inflammation, β-cell stress, or all three) in the pathogenesis of type 1 diabetes and their impacts on age at diagnosis.
Our study highlights the significance of the relationship between the TCF7L2 polymorphism, a person's age at onset of obesity and the prevalence of T2D, and confirms lower adiponectin levels in obese diabetics in comparison to obese nondiabetics.
When stratified by diabetic or obesity status, significant associations between TCF7L2 polymorphism and CRC risk were limited to non-diabetic or normal-weight subjects.
In conclusion, we provide strong evidence supporting the need for considering obesity when analyzing the TCF7L2 effects and propose the use of obesity-specific GRS for T2D.
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.
Moreover, 18 obesity and 21 type 2 diabetes candidate genes had CpG sites with differences in adipose tissue DNA methylation in response to exercise (q<0.05), including TCF7L2 (6 CpG sites) and KCNQ1 (10 CpG sites).
We investigated the effects of obesity surgery-induced weight loss on transcription factor 7-like 2 gene (TCF7L2) alternative splicing in adipose tissue and liver.
The type 2 diabetes-associated variant in TCF7L2 is associated with latent autoimmune diabetes in adult Europeans and the gene effect is modified by obesity: a meta-analysis and an individual study.
The observed trends of obesity risk alleles for risk of stroke/TIA as well as the possible sex-specific differences in clinical outcomes found for the TCF7L2 (rs7903146) require replication in future studies.
In the "obese-type 2 diabetes" scan, FTO variants had the strongest type 2 diabetes effect (rs8050136: relative risk [RR] 1.49 [95% CI 1.34-1.66], P = 1.3 x 10(-13)), with only weak evidence for TCF7L2 (rs7901695 RR 1.21 [1.09-1.35], P = 0.001).
We genotyped the TCF7L2 single nucleotide polymorphisms rs7903146 and rs12255372 (previously associated with type 2 diabetes) and rs10885406 and rs7924080 (which tag haplotype A [HapA], a haplotype reported to be associated with obesity) in 2,512 FHS participants.
The association of 17 candidate single nucleotide polymorphisms (SNPs) in IL10 and other immune response genes (CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and genes related to obesity (PPARG, TCF7L2, ADIPOQ, LEP) with colorectal cancer was investigated.
Polymorphisms in TCF7L2 (rs7903146, OR 1.10, 95% CI 1.04-1.17, p = 0.00097), FTO (rs9939609, OR 1.08, 95% CI 1.02-1.14, p = 0.0065), WFS1 (rs10010131, OR 1.07, 95% CI 1.02-1.13, p = 0.0078) and IGF2BP2 (rs4402960, OR 1.07, 95% CI 1.01-1.13, p = 0.021) predicted the development of at least three components of the metabolic syndrome in both univariate and multivariate analysis; in the case of TCF7L2, WFS1 and IGF2BP this was due to their association with hyperglycaemia (p < 0.00001, p = 0.0033 and p = 0.027, respectively) and for FTO it was due to its association with obesity (p = 0.004).
We studied the TCF7L2 messenger RNA (mRNA) expression in paired samples of visceral and subcutaneous adipose tissue from 49 subjects using quantitative real-time polymerase chain reaction and its relation to obesity and T2DM.
Recent genome-wide association studies have identified six novel genes for type 2 diabetes and obesity and confirmed TCF7L2 as the major type 2 diabetes gene to date in Europeans.
To evaluate whether the five reported risk variants confer a higher risk for obesity and early impairment of glucose metabolism in children, we genotyped these risk variants of the TCF7L2 gene in a representative cohort of 1029 Caucasian children and an independent cohort of 283 obese children.