Genetic Variation in the Bitter Receptors Responsible for Epicatechin Detection Are Associated with BMI in an Elderly Cohort

Abstract

Globally, more than one-third of adults are overweight. Overweight and obesity are complex and multifaceted conditions, associated with an increased risk of chronic illness and early mortality. While there are known risk factors, these alone do not fully explain the varying outcomes between individuals. Recently, taste receptors have been proposed to have a role in the risk for obesity. These receptors are expressed throughout the gastrointestinal tract. In this system, they may be involved in modulating dietary intake and metabolic processes. The taste 2 family of receptors (T2Rs) detects bitter compounds. Receptors T2R4 and T2R5 detect (-)-epicatechin (epicatechin), an antioxidant polyphenol, which may have protective effects against obesity. However, the potential role for taste receptors in this association has not been explored. This study assessed whether polymorphisms in TAS2R4 (rs2233998 and rs2234001) and TAS2R5 (rs2227264) were associated with body mass index (BMI). Genotyping (Taqman qPCR assays) was performed on DNA extracted from blood samples (n = 563) from an elderly cohort. Homozygosity for the minor allele of all polymorphisms was significantly associated with a lower BMI in males. The TAS2R4-rs2233998 CC genotype, the TAS2R4-rs2234001 CC genotype and the TAS2R5-rs2227264 TT genotype were associated with lower BMI (2.1, 2.1 and 2.2 units; p = 0.002, 0.003 and 0.001, respectively). Epicatechin intake was not associated with BMI and genotype was not associated with epicatechin intake. This suggests that the association between TAS2R genotype and elevated BMI risk occurs through altered extra-oral responses and not directly via altered epicatechin intake.

Functional and genomic comparative study of the bitter taste receptor family TAS2R: Insight into the role of human TAS2R5

“…It is unclear from the present data whether the variation in coffee bitterness seen for this haplotype results from the functional alteration of T2R5 or influences on transcription that alters the expression 36 . Additionally, recent studies in this allele have revealed that TGAG homozygotes show a significantly lower body mass index 37 38 .…”

“…36 Additionally, recent studies in this allele have revealed that TGAG homozygotes show a significantly lower body mass index. 37 The bitterness of alcohol is known to be the major taste component that influences alcohol consumption. 38 Choi et al showed an association between the TAS2R5 rs2227264 variant and total alcohol intake.…”

Effect of Phenolic Compounds on Human Health

“…Furthermore, this book also included a cross-sectional study to investigate the multidirectional interactions between TAS2R genotype [TAS2R4 gene (rs2233998 and rs2234001); TAS2R5 gene (rs2227264)], epicatechin intake, and body mass index (BMI), together in an elderly cohort. This study demonstrated that there is not an association between epicatechin intake and BMI and TAS2R genotype [8].…”

A Cross-Sectional Study of Bitter-Taste Receptor Genotypes, Oral Health, and Markers of Oral Inflammation

“…These significant associations may suggest relevance for bitter-taste receptor genotype in the modulation of innate immunity and inflammatory pathways [29,30,34,[37][38][39]. Moreover, the bitter agonist, epicatechin (detected by TAS2R4-rs2234001 and TAS2R5-rs2227264 [53]), may be associated with the modulation of inflammatory pathways [60]. However, further studies are needed to evaluate these associations in oral inflammation.…”

“…The DNA samples were stored at −20 • C before genotyping. Genotyping was completed via qPCR (QuantStudio 7 Flex Real-Time PCR) with TaqMan SNP Genotyping assays (Applied Biosystems™, Thermo-Fisher Scientific, Waltham, MA, USA) and TaqMan™ Genotyping Master mix as per the TaqMan™ user's guide [52,53]. Complete genotyping was a mandatory inclusion criterion for this study.…”