TCF7L2 Gene and T Allele’s impact on Type 2 Diabetes

Saptaparna Dasgupta, Bennett University

Type 2 diabetes is an impairment known to hamper the body’s ability to regulate and utilize sugar (glucose) as fuel. It is a chronic disease in which there is too much sugar in the blood. Type 2 diabetes can eventually lead to cardiovascular, neurological, and immune system problems. A prominent cause of worldwide mortality, type 2 diabetes is attributed to dietary variables and heredity. According to recent studies, the most significant genetic contribution is a single variant in the TCF7L2 (rs7903146) gene. However, it has not been studied in a healthy population using the proven long-term biomarker of glucose control, glycated hemoglobin (HbA1c).  The study by Podboi et al. 2021 is based on the investigation of the genetic polymorphism associated with rs7903146 and dietary consumption in a population with Type 2 diabetes. 

Risks associated with type 2 diabetes:

Worldwide, it is predicted that 463 million individuals have type 2 diabetes and 347 million have impaired glucose tolerance, resulting in 4.2 million deaths in 2019. It is estimated that 10 percent (or USD 760 billion) of worldwide health expenditures are spent on diabetes treatment and management. Insulin production by pancreatic beta cells and a proper tissue response are required for glucose uptake to occur physiologically.

A reduction in glucose absorption and reduced beta-cell activity occur in circumstances of increased free fatty acids. All of these factors contribute to insulin resistance and increased blood glucose levels, which lead to the development of type 2 diabetes. Weight gain and obesity are two of the most important risk factors for type 2 diabetes that may be modified. Other risk factors for the illness include physical activity, age, family history, ethnicity, and nutrition, which are independent of body weight.

TCF7L2 (rs7903146) gene:

It has been depicted about genetic predispositions have also been linked to type 2 diabetes. Type 2 diabetes is linked with 139 common variations, according to a recent meta-analysis of genome-wide association studies (GWAS). There were 2,892 cases and 596,424 controls in this meta-analysis, and the most significant variation was rs7903146 in the TCF7L2 gene. rs7903146 was also found as the most important genetic variation in connection to diabetes in previous meta-analyses.

On the TCF7L2 gene, rs7903146 is an intron polymorphism with a minor allele frequency of 0.23 across all populations and 0.32 among Europeans. Non-dietary environmental variables, such as stress and physical exercise, might impact such measurements. This alternate biomarker offers an estimate of a person’s average blood glucose level over the past 60–90 days and is less susceptible to acute environmental influences than glycated hemoglobin. T2D risk was shown to be less volatile with HbA1c in a meta-analysis of the GWAS study.

How was the study conducted?

A population of 74 Caucasian participants was appointed for the study by Podboi et al. 2021. The required parameters like height, weight, waist, and chest circumference were measured of the respective participants. According to the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk validated Food Frequency Questionnaire, dietary intake was calculated using the FETA platform. Followed by which the hemoglobin levels were measured by collecting the capillary blood from earlobes and fingertips. Furthermore, DNA analysis of the participants was carried out by collecting their saliva samples.

Outcome of the study:

The genotypes were divided into CC and CT/TT groups, where the T allele represents the carrier and CC stands for homozygous participants. For the T-carrier mean HbA1c levels were 2.1 mmol/mol higher than CC group mean HbA1c levels when HbA1c levels were presented as departures from the general mean Nearly 70 percent (n = 22) of T carriers had HbA1c levels above average, compared to 40 percent (n = 15) of CC carriers (p = 0.022). In a multivariate linear regression analysis, the impact of genotype and diet on HbA1c levels was determined. Multicollinearity did not exist for any of these variables (tolerance values >0.1).

Discussion:

In several groups, the TCF7L2 gene (rs7903146) has been linked as a major genetic susceptibility to T2D. T allele carriers had increased nocturnal glucose, which indicates poor blood glucose control, especially in individuals with more body fat and weight. The findings in this study show new correlations between protein and total carbohydrate consumption and HbA1c levels. It’s unclear if protein and carbohydrate consumption affects the TCF7L2 polymorphism’s influence on type 2 diabetes risk. To determine if genetic susceptibility is a co-factor, more study is needed. The study was designed to look for links between type 2 diabetes and genetics and nutrition.

Significance of the study:

HbA1c is used to indicate long-term blood homeostasis, which reduces misdiagnosis. This might lower healthcare expenditures and other disease-related health concerns. The study confirmed previous findings that the TCF7L2 gene (rs7903146) polymorphism has a genetic influence on type 2 diabetes in healthy individuals who carry the risk-allele. Carbohydrate, protein, SFA, and MUFA intakes appear to be linked to HbA1c levels in the diet.

Also read: Evolution of adaptive traits – Natural Selection?

Reference:

1. Podboi, I. C. R., Stephenson, S., Pilic, L., Graham, C. A.-M., King, A., & Mavrommatis, Y. (2021). Dietary intake and tcf7l2 rs7903146 t allele are associated with elevated blood glucose levels in healthy individuals. Lifestyle Genomics, 1–7. https://doi.org/10.1159/000518523

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Author info:

Saptaparna Dasgupta, currently a B. Tech 3^rd year student, pursuing Biotechnology, is a diligent student and determined in terms of her career goals. Being a budding biotechnologist, she is open to all research fields of her course and passionate about knowledge. She is focused and constantly tries to improve her writing skills, also a project enthusiast and is fond of gaining hands-on experience in laboratories. She believes that all hard works and effort pay off eventually and follows this as the motto of her life.