Effects of the genetic polymorphisms of <i>TAS2R43</i> and <i>TAS2R46</i> on receptors’ function and on perceived bitterness of caffeine by human subjects

We investigated the effects of coding single-nucleotide polymorphisms (SNPs) in bitter taste receptors TAS2R43 and TAS2R46 on their predicted structural stability, cellular functions, and human threshold for bitterness of caffeine. We found differences in the cell surface expression and reaction to caffeine among the haplotypes of TAS2R43 and -46 protein. Ancestral haplotypes of the proteins showed higher response to caffeine than derived haplotypes both for TAS2R43 and -46, which were also predicted to be less structurally stable and showed lower expression at the cell surface membrane. There was a significant difference in human bitter perception of caffeine between people with different TAS2R43 genotypes. Considering the functional differences based on their genotypes and the distribution of the haplotypes in the regions, these SNPs may relate to the sensitivity to several bitter compounds, which correlated with human evolution spread from Africa.