Weight Loss Genetics – TCFL72 variants

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…

  • Inheriting the TCF7L2 variants from your mother instead of your father may increase your risk of diabetes.  [ref]
  • TCF7L2 variants also influence risk of gestational diabetes. [ref]

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