Association analysis of bitter receptor genes in five isolated populations identifies a significant correlation between TAS2R43 variants and coffee liking

Nicola Pirastu; Maarten Kooyman; Michela Traglia; Antonietta Robino; Sara M Willems; Giorgio Pistis; Pio d'Adamo; Najaf Amin; Angela d'Eustacchio; Luciano Navarini; Cinzia Sala; Lennart C Karssen; Cornelia van Duijn; Daniela Toniolo; Paolo Gasparini

doi:10.1371/journal.pone.0092065

Association analysis of bitter receptor genes in five isolated populations identifies a significant correlation between TAS2R43 variants and coffee liking

PLoS One. 2014 Mar 19;9(3):e92065. doi: 10.1371/journal.pone.0092065. eCollection 2014.

Authors

Affiliations

¹ Institute for Maternal and Child Health, Istituto Di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo," Trieste, Italy; Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
² Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
³ Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy.
⁴ Institute for Maternal and Child Health, Istituto Di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo," Trieste, Italy.
⁵ illycaffè s.p.a, Trieste, Italy.
⁶ Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Centre for Medical Systems Biology, Leiden University Medical Center, Leiden, The Netherlands.

Abstract

Coffee, one of the most popular beverages in the world, contains many different physiologically active compounds with a potential impact on people's health. Despite the recent attention given to the genetic basis of its consumption, very little has been done in understanding genes influencing coffee preference among different individuals. Given its markedly bitter taste, we decided to verify if bitter receptor genes (TAS2Rs) variants affect coffee liking. In this light, 4066 people from different parts of Europe and Central Asia filled in a field questionnaire on coffee liking. They have been consequently recruited and included in the study. Eighty-eight SNPs covering the 25 TAS2R genes were selected from the available imputed ones and used to run association analysis for coffee liking. A significant association was detected with three SNP: one synonymous and two functional variants (W35S and H212R) on the TAS2R43 gene. Both variants have been shown to greatly reduce in vitro protein activity. Surprisingly the wild type allele, which corresponds to the functional form of the protein, is associated to higher liking of coffee. Since the hTAS2R43 receptor is sensible to caffeine, we verified if the detected variants produced differences in caffeine bitter perception on a subsample of people coming from the FVG cohort. We found a significant association between differences in caffeine perception and the H212R variant but not with the W35S, which suggests that the effect of the TAS2R43 gene on coffee liking is mediated by caffeine and in particular by the H212R variant. No other significant association was found with other TAS2R genes. In conclusion, the present study opens new perspectives in the understanding of coffee liking. Further studies are needed to clarify the role of the TAS2R43 gene in coffee hedonics and to identify which other genes and pathways are involved in its genetics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Coffee*
Genetic Association Studies*
Humans
Polymorphism, Single Nucleotide / genetics*
Receptors, G-Protein-Coupled / genetics*
Taste / genetics*

Substances

Coffee
Receptors, G-Protein-Coupled
taste receptors, type 2

Grants and funding

The SR study has been funded by the Region Friuli Venezia Giulia grant number 35\09 Linea 2 “Sulle tracce di Marco Polo: geni, gusto e loro implicazioni sulla salute lungo la Via della Seta”. The INGI-FVG study was funded through the Italian Ministry of health. This work is part of a joint project with illycaffè s.p.a. within the framework of the “Nutrigenomica e consumo di caffè: effetti fisiologici, genetica del gusto e genetica della pianta” project partially supported by the POR-FESR 2007-2013 Regione Autonoma Friuli Venezia Giulia, Italy. The VB study was founded trough Fondazione Compagnia di San Paolo, Torino, Fondazione Cariplo, Milano and Health Ministry (Progetto Finalizzato and Italian Centre for Disease Prevention and Control). The ERF study as a part of EUROSPAN (European Special Populations Research Network) was supported by European Commission FP6 STRP grant number 018947 (LSHG-CT-2006-01947) and also received funding from the European Community's Seventh Framework Programme (FP7/2007-2013)/grant agreement HEALTH-F4-2007-201413 by the European Commission under the programme "Quality of Life and Management of the Living Resources" of 5th Framework Programme (no. QLG2-CT-2002-01254). High-throughput analysis of the ERF data was supported by joint grant from Netherlands Organisation for Scientific Research and the Russian Foundation for Basic Research (NWO-RFBR 047.017.043). Statistical analyses were partly carried out on the Genetic Cluster Computer (http://www.geneticcluster.org) which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003 PI: Posthuma) along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. This research was financially supported by BBMRI-NL, a Research Infrastructure financed by the Dutch Government (NWO 184.021.007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.