SNP variation in the bitter taste TAS2R38 gene evaluated in student populations of several italian universities and isolates

Abstract

People vary widely in their sensitivities to bitter compounds, but the all intercorrelation of these sensitivities is unknown. The study of genetic influences on bitter taste perception originated from the discovery in the 1930s that some individuals had taste to phenylthiocarbamide(PTC), whereas others found it extremely bitter. Subsequently, many studies were carried out on PTC and the structurally related compound propylthiouracil (PROP) to assess this viability and to determine the root causes. Initial family studies strongly suggested that PTC no tasting was due to a recessive allele in a single gene and heritability was estimated at 0,5. 55-85% of variation in PTC detection. The PTC gene, TAS2R38 on chromosome 7, consists of a small, single coding exon 1002 bp. The non-tester allele differs from the tester one for three single nucleotide polymorphisms (SNPs) at position 49, 262 and 296 in the gene, determining two predominant haplotypes. The phenotypic assay to differentiate taster from non-taster is relatively easy and quick, as well as the genotyping of the known polymorphisms. Therefore, this phenotypic-genotypic assay results to be particularly suitable for molecular and population genetic studies on large populations and for teaching genetics at university and high school level by allowing students to assess the genotype-phenotype relationship on themselves. By providing students with paper samples soaked in different solutions of PTC and PROP it was been possible to assess the individual threshold of bitterness sensitivity. DNA was extracted from saliva by means of Qiagen Kit mini, and following PCR amplification, polymorphisms were evaluated by gel electrophoresis. We started to develop this assay involving hundreds of students of several Italian universities such as Caltanissetta, Palermo, Catania, Cosenza in the South of Italy, Pisa and Parma in the Centrum of Italy with the aim to describe the Italian population for this polymorphism. By considering the large number of samples, we expect to be able to assess the frequency of additional rare polymorphisms, possibly further characterizing defined populations. A detailed questionnaire concerning life style and diet was also administered to students for possible association studies with the genetic polymorphism. Moreover, investigations on isolated populations such as these leaving in mountains of Garfagnana (Lucca) was undertaken. The distribution frequency of TAS2R38 polymorphisms in different sub sets of Italian population and isolates, the possible relationship with food preferences and other life styles, such as alcohol drinking and smoking will be reported and discussed. Functional expression studies demonstrate that five different haplotypes from the hTAS2R38 gene, code for operatively distinct receptors. The responses of the three haplotypes we also tested in vivo correlate strongly with individuals' psychophysical bitter sensitivities to a family of compounds. These data provide a direct molecular link between heritable variability in bitter taste perception to functional that contain the N-C= moiety. The molecular mechanisms of perceived bitterness variability have therapeutic implications, such as helping patients to consume beneficial bitter-tasting compounds, for example, pharmaceuticals and selected phytochemicals (Bufe 2005). Our goal is to investigate correlations as a function of individual sensitivities to several bitter compounds representative of different chemical classes and, from these correlations, infer the number and variety of potential bitterness transduction system.