TAS1R2 Gene Detail

Taste perception is considered an essential determinant of food acceptance, food selection and ultimately the establishment of dietary habits. Although the preference of sweet taste seems an innate quality, genetic differences in sweet taste detection seems to influence the intensity of the sweet experience as well as the frequency of sweet food consumption. Thus, it does not only impact eating behaviour but also nutritional status.

The extent to which genetic variation influences taste and resultant eating habits seem to be influenced by environmental and cultural experiences, with children showing a stronger correlation between genetic predisposition for certain eating behaviours and their actual consumption patterns. While not consistently found, several studies on the genetics of taste suggest that learned behaviours can override genetic predisposition – potentially explaining why in adults, environmental and/or cultural experiences rather than genetic predisposition appear more closely correlated to taste perception and eating behaviour.

The Ile191Val polymorphism reportedly increase preference for sweet foods, although potential ethnic differences have been found. It may seemingly predispose to an additional difficulty and / or reluctance in changing eating behaviour to reduce sugar consumption.

It is deemed important to determine individual genetic susceptibility to sweet preference as this may promote eating behaviour that raises the risk for adiposity, metabolic disturbances and dental caries.

TAS1R2 Ile191Val A>G

The rs35874116 polymorphism, located in exon 3 of the TAS1R2 gene, causes a nucleotide substitution at position 571 where Adenine is substituted with Guanine (A571G). This non-synonymous polymorphism, which leads to an amino acid substitution at position 191 (Ile191Val) is purportedly located in the N-terminal extracellular domain of the receptor, responsible for binding ligands to be tasted. The Ile191 (A) variant is reportedly associated with an increased preference for sweet foods. The TAS1R2 gene is said to be within the top 5-10% of all human genes with regards to the reported number of polymorphisms,  thus it may explain much of the inter-individual differences with regards to sweet preference.    

A study considering two diverse Canadian populations of men and women, reported that the Ile191Val polymorphism significantly influenced the habitual consumption of sugar in overweight and obese participants. In the first healthy and young adult population, Ile/Ile homozygotes with a BMI ≥ 25 kg/m² reported consuming more carbohydrates (including fibre and sugars) over a 1-month period when compared to Val-carriers. Interestingly, fruit consumption was also lower in Val-carriers as compared to those homozygous for Ile. Research has however found that fruit consumption is more strongly correlated to sweet snack consumption than to vegetable consumption.

In the second population of overweight and obese type 2 diabetic individuals, fasting insulin concentrations were significantly lower in Val-carriers compared to those homozygous for Ile. After receiving dietary counselling in line with the Canadian Diabetes Association (CDA) guidelines recommending a limit for added sugar intake at ≤ 10% of daily energy, no dietary changes were observed in Ile-homozygotes whereas Val-carriers demonstrated a significant decrease in sugar consumption. Following the results from population 2, the authors suggested that the Ile191Val polymorphism may influence the success or failure of changing dietary intake and adopting new lifestyle choices in response to dietary advice. 

In contrast to the abovementioned studies, a cross-sectional study from Ramos-Lopez et al. (2016) reported that among 441 Mestizos subjects from West Mexico, Val/Val homozygotes had a significantly higher intake of total carbohydrates (including fibre, cereals and also vegetables) while additionally, they had significantly elevated triglyceride levels when compared to Ile-carriers. The authors suggested that this difference may be attributed to ethnic differences among populations, gene-diet interactions, mode of inheritance and food culture. Although the traditional Mexican diet contained a wide variety of wild and domestic crops, the current-day obesogenic environment in Mexico has said to promote the substitution of the natural, traditional “tortilla” for high-fat industrialised cereals in the form of sweet bread and pastries. The observed dyslipidemia (as elevated triglycerides) was also ascribed to the high intake of carbohydrates (> 55% total energy) as an increase in insulin concentration is said to cause a shift from fatty acid oxidation to triglyceride synthesis.     

The threshold of sweet perception also seems to be influenced by leptin concentration as leptin can reportedly interfere and affect the signal transduction for sweet taste detection. It is thus proposed that a difference in sweet taste perception may not only be due to genetic differences in the sweet taste receptor, but also due to the influence of adiposity and potentially the time of day. In terms of the time of day, it is suggested that, as the leptin concentration naturally increases with the passing of the day, the sweet taste threshold also increases.

In terms of adiposity, it has been determined that overweight and obese individuals have elevated leptin concentrations and that BMI can be used as a marker for leptin. As Eny et al. (2010) predicted, a significant interaction between the Ile191Val genotype and sugar consumption only occurred in participants with a BMI ≥ 25. The authors proposed that this could be due to a loss of the normal synchronisation between the rising levels of leptin and recognition thresholds that would occur in lean subjects or it could be due to a state of leptin resistance that occurs in overweight and obese individuals. The effect of leptin on the suppression of sugar detection was proposed to saturate at a much lower rate (15-20 ng/ml) than the leptin concentrations reported for overweight and obese individuals. Previous studies have indeed reported that genetic variation in leptin and leptin-receptor genes associated with sweet preference. Similar interactions with BMI were reported when sweet taste detection, as measured by perceived sweetness, was inversely associated with BMI in university students and when a review found that the daytime variation for sweet recognition thresholds disappeared in individuals with BMI > 25.         

It has been suggested that the TAS1R2 gene may interact with GLUT2. Because TAS1R2 is also expressed in the GIT, pancreas, and hypothalamus, which follows a similar distribution of tissue expression as GLUT2, the sweet taste receptor may act through these pathways to affect food intake potentially through a glucose-sensing mechanism. It has previously been reported that GLUT2 may be associated with sugar consumption and that it responds to sweet-taste receptor signalling in the GIT.

For Ile191-carriers (or A-allele carriers; in some research interchangeably noted as the T-allele), it might be an important consideration to limit total carbohydrate and sugar intake. It might be considered particularly difficult for those with a genetic predisposition for sweet taste preference, thus practicing mindful eating and establishing a supportive environment, particularly for overweight and obese individuals, may be essential tactics for weight management.