Allelic polymorphism within the TAS1R3 promoter is associated with human taste sensitivity to sucrose
| Autor: | Christopher T. Simons, Jay Patrick Slack, Alexey A. Fushan, Dennis Drayna, Ani Manichaikul |
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| Rok vydání: | 2009 |
| Předmět: |
EVO_ECOL
Sucrose Genotype Transcription Genetic Black People Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology White People Article Receptors G-Protein-Coupled TAS1R3 TAS1R2 Asian People Transcription (biology) Coding region Humans Allele Luciferases Promoter Regions Genetic Gene Alleles Genetics Analysis of Variance Agricultural and Biological Sciences(all) Biochemistry Genetics and Molecular Biology(all) Taste Perception Molecular biology Area Under Curve General Agricultural and Biological Sciences |
| Zdroj: | Current biology : CB. 19(15) |
| ISSN: | 1879-0445 |
| Popis: | Human sweet taste perception is mediated by the heterodimeric G-protein coupled receptor complex encoded by the TAS1R2 and TAS1R3 genes [1-7]. The extent of variation in these genes has been recently characterized [8], but the functional consequences of such variation are unknown. In this study we report that two C/T single nucleotide polymorphisms located at positions −1572 (rs307355) and −1266 (rs35744813) upstream of the TAS1R3 coding sequence strongly correlate with human taste sensitivity to sucrose, and explain 16% of population variability in perception. Individuals who carry T alleles display reduced sensitivity to sucrose compared to those who carry C alleles at these nucleotide positions. Using a luciferase reporter assay, we demonstrate that the T allele of each SNP results in reduced promoter activity in comparison to the C alleles, consistent with the phenotype observed in humans. We also found that the TAS1R3 promoter region extending from position −1700 to −1000 harbors a novel composite cis-acting element that has a strong silencing effect on promoter activity. We conclude that the rs307355 and rs35744813 SNPs affect gene transcription by altering the function of this regulatory element. A worldwide population survey reveals that the T alleles of rs307355 and rs35744813 occur at lowest frequencies in European populations. We propose that inherited differences in TAS1R3 transcription account for a substantial fraction of worldwide differences in human sweet taste perception. |
| Databáze: | OpenAIRE |
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