TAS2RS BITTER TASTE GENES AND HUMAN VARIABILITY IN BEHAVIOR, DISEASE SUSCEPTIBILITY AND LONGEVITY

Initially, this work is focused on role of the polymorphic bitter taste gene, TAS2R38, involved in the perception of the bitter synthetic chemical phenylthiocarbamide (PTC), in food preference life style, as alcohol and smoke intake. We have considered a sample 1706 university students (17-25 years old) from different part of Italy: Palermo, Catania Cosenza and Caltanissetta University (South Italy); Pisa, Lucca, Terni and Roma University (Centre Italy); Parma and Brescia University( North Italy). They have been enrolled in the study. PTC “Taster” and “Non Taster” subjects were discriminated by means of tasting soaked papers in PTC different solutions. DNA was extracted from saliva, and genotyped by TaqMan assay for of TAS2R38 SNPs (Single Nucleotide Polymorphism) A possible association between genotype and food preference was assessed by administering a detailed questionnaire. Our Results shown: 1) the entire population was found to be in Hardy –Weimberg equilibrium. 2) No significant difference in allele frequencies between Centre and South Italy was observed, while significant differences between genotype distribution and European population as Germany, Czchoslovakia and Italy. 3) A good correlation (80%) between TA2R38 polymorphism and capability to assess PTC bitterness was observed. 4) A non statistically significant correlation between smoke intake and genotype, instead significant correlation between alcohol intake and genotype,(p=0.03).5) we have no found statistically significant indication that TA2R38 polymorphism (genotype) is associated with the preference of some food. Since previous reports showed a modest association between greater sensitivity to PROP and a higher number of colonic polyps, suggesting that PROP status could provide a link between vegetable intake and colon cancer risk, we have considered a study of cases-control, from Germany and Czech Republic. Cases are positive colonoscopic results for malignancy, histologically confirmed as colon or rectal carcinomas. we found no statistically significant association between TAS2R38 SNPs and colorectal cancer risk, considering major TAS2R38 genotypes: Chi-squared=4.65 and p=0.097 and rare genotype, Chi-squared=0.73 and p=0.95.Molecular sensing of luminal contents also initiates hormonal and/or neural pathways leading to the regulation of caloric intake, pancreatic insulin secretion, and metabolism TAS2R14 has been shown to be activated by various substances, several of which are powerful toxic agents like picrotoxin and aristolochic acid which is a strong carcinogen. In the same case-control study, we have explored also the role of three tagging polymorphisms in the TAS2R14 gene, in conclusion we can confidently exclude a major role for common polymorphisms of the TAS2R14 gene in colorectal cancer risk in this population. Other published report shown that bitter taste receptors are also expressed in subsets of cells within the mammalian gastrointestinal tract, where they mediate nutrient assimilation and endocrine responses, suggesting that a functionally compromised TAS2R receptor negatively impacts glucose homeostasis, providing an important link between alimentary chemosensation and metabolic disease. We started to investigate the possible influence of TAS2Rs genes on longevity, considering a elderly elderly (60-104) population of South Italy, and we have found a statistically significant association between TAS2R16 polymorphism: rs978739 and aging; (p<0.001), a statistically significant association between other TAS2R16 polymorphism: rs6466849 with blood level of cholesterol (p=0.01), further we have found a statistically significant association between TAS2R46 polymorphism: rs2708380 and BMI; Chi-squared=17.23 and p=0.0085. There reasons are unclear so, our goal is confirmed and clarify if TAS2R16 SNPs are same effect rispectively on age and blood level cholesterol, well as TAS2R46 polymorphism: rs2708380 influence BMI level.