TCF7L2 – transcription factor 7-like 2 gene – is involved in beta cells in the pancreas which produce insulin as well as being involved in adipocytes (fat cells) and metabolic syndrome. It is a part of the Wnt signaling pathway, which passes signals into cells through surface receptors.
Variants in TCFL2 are tied to type-2 diabetes, obesity, higher BMI, and larger waist circumference. The SNPs listed below have been found to up-regulate TCF7L2 in pancreatic beta cells [ref] The up-regulation is thought to impair insulin secretion from the beta cells rather than causing insulin resistance. [ref] [ref]
A 2014 study on how TCF7L2 influences the risk of type-2 diabetes found that it regulates proinsulin and its formation into insulin. In addition to the effect on proinsulin production in ISL1, the study also found that:
” Although the mechanisms by which the variant in SLC30A8 increases risk of T2D are not clear, recent data suggest that reduction in zinc concentrations in the portal vein after β-cell-specific disruption of Slc30a8 might influence hepatic insulin clearance (49). If confirmed, this would suggest that TCF7L2 might influence all key steps in (pro)insulin synthesis, processing and clearance.” [ref]
Genetic Variants in TCF7L2:
rs7903146 (T is the minor allele)
- impaired insulin secretion, type 2 diabetes risk[ref]
- higher intake of omega-6 polyunsaturated fats caused T allele carriers to have higher fasting glucose and a higher risk of metabolic syndrome. [ref]
rs12255372 (T is the minor allele)
- While carbohydrate intake made no difference, glycemic index and glycemic load being high caused an increased risk for TT individuals in regards to metabolic syndrome[ref]
- Those on a low-fat diet lost more weight with the TT genotype. [ref]
- Hispanics with the minor allele have a lower avg BMI, thus showing that the effects could be population specific since most of the larger studies were predominantly Caucasian European populations. [ref]
rs4506565 (T is the minor allele)
- type 2 diabetes risk [ref]
- higher risk of new-onset type-2 diabetes when on hydrochlorothiazide [ref]
rs3814570 (minor allele is T)
- also associated with Crohn’s disease [ref]
Possible solutions for weight loss:
- Cut out omega-6 polyunsaturated fats such as sunflower, safflower, corn, cottonseed, sesame, soybean and peanut oils.
- Watch your glucose levels and look into a lower glycemic index diet.
- Check your zinc levels and supplement with zinc if needed.
Interesting to note…