Nonsynonymous single nucleotide polymorphisms in human tas1r1, tas1r3, and mGluR1 and individual taste sensitivity to glutamate

Several studies indicate an essential role of the heterodimer Tas1R1-Tas1R3 for monosodium l-glutamate (MSG) detection, although others suggest alternative receptors. Human subjects show different taste sensitivities to MSG, and some are unable to detect the presence of glutamate. Our objective was to study possible relations between phenotype (sensitivity to glutamate) and genotype (polymorphisms in candidate glutamate taste receptors tas1r1, tas1r3, mGluR4, and mGluR1) at the individual level. The sensitivity was measured with a battery of tests to distinguish the effect of sodium ions from the effect of glutamate ions in MSG. A total of 142 genetically unrelated white French subjects were categorized into 27 nontasters (specific ageusia), 21 hypotasters, and 94 tasters. Reverse transcriptase polymerase chain reaction and immunohistochemistry showed expression of tas1r1, tas1r3, and alpha-gustducin in fungiform papillae in all 12 subjects tested, including subjects who presented specific ageusia for glutamate. Amplification and sequencing of cDNA and genomic DNA allowed the identification of 10 nonsynonymous single nucleotide polymorphisms (nsSNPs) in tas1r1 (n = 3), tas1r3 (n = 3), and mGluR1 (n = 4). In our sample of subjects, the frequencies of 2 nsSNPs, C329T in tas1r1 and C2269T in tas1r3, were significantly higher in nontasters than expected, whereas G1114A in tas1r1 was more frequent in tasters. These nsSNPs along with minor variants and other nsSNPs in mGluR1, including T2977C, account for only part of the interindividual variance, which indicates that other factors, possibly including additional receptors, contribute to glutamate sensitivity.