Refining associations between TAS2R38 diplotypes and the 6-n-propylthiouracil (PROP) taste test: findings from the Avon Longitudinal Study of Parents and Children
BMC Genetics
Refining associations between TAS2R38 diplotypes and the 6-n-propylthiouracil (PROP) taste test: findings from the Avon Longitudinal Study of Parents and Children
Nicholas J Timpson 2 3
Jon Heron 1
Ian NM Day 2
Susan M Ring 2
Linda M Bartoshuk 0
Jeremy Horwood 2
Pauline Emmett 1
George Davey- Smith 2
0 University of Florida, Dept. of Community Dentistry and Behavioral Science , Gainesvile , USA
1 ALSPAC, Department of Social Medicine, Bristol University , Bristol , UK
2 Department of Social Medicine, Bristol University , Bristol , UK
3 The Wellcome Trust Centre for Human Genetics, Oxford University , Oxford , UK
Background: Previous investigations have highlighted the importance of genetic variation in the determination of bitter tasting ability, however have left unaddressed questions as to within group variation in tasting ability or the possibility of genetic prescription of intermediate tasting ability. Our aim was to examine the relationships between bitter tasting ability and variation at the TAS2R38 locus and to assess the role of psychosocial factors in explaining residual, within group, variation in tasting ability. Results: In a large sample of children from the Avon Longitudinal Study of Parents and Children, we confirmed an association between bitter compound tasting ability and TAS2R38 variation and found evidence of a genetic association with intermediate tasting ability. Antisocial behaviour, social class and depression showed no consistent relationship with the distribution of taste test scores. Conclusion: Factors which could influence a child's chosen taste score, extra to taste receptor variation, appeared not to show relationships with test score. Observed spread in the distribution of the taste test scores within hypothesised taster groups, is likely to be, or at least in part, due to physiological differentiation regulated by other genetic contributors. Results confirm relationships between genetic variation and bitter compound tasting ability in a large sample, and suggest that TAS2R38 variation may also be associated with intermediate tasting ability.
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Background
Variation in the ability to taste PTC, PROP and related
compounds has been recognised as one of the classical
markers of population genetics. Since the seminal
findings of Blakeslee and Fox [1,2], the distribution of PTC/
PROP tasting has been extensively analysed. This
variation has been noted to vary from the extremes of "taste
blindness" (a lack of sensitivity, or non-taster of PTC/
PROP), to apparent "super tasting" (an extra sensitive
reaction to the bitterness of PTC/PROP) and has shown
marked variation in the distribution of such traits across
populations (taste blindness ranging from 3% in West
Africa, to 623% in China, 40% in India and around 30%
in North American Caucasian populations [3,4]).
Conventional assessment of bitter tasting ability has been
by PTC (phenylthiocarbamide)/PROP taste challenge and
response assessment. It was found that all bitter
compounds containing the thiocyanate (N-C = S) moiety elicit
bimodal patterns of response [5]. In addition to this it has
been shown that PTC taste responses are strongly
correlated with all of these compounds [6], as is the case for
PROP [3].
Initial genetic analyses presented indications of bitter
compound tasting ability as a complex genetic trait, but
provided little specific evidence as to possible causal, or
robustly associated genetic components [4,7-11].
However, specific positional cloning efforts have since
identified a region of chromosome 7 (in the TAS2R38 gene),
which has shown patterns of haplotypic association
which are associated with specific measurements of bitter
tasting ability [12]. This has provided direct evidence of a
physiological link between genetic variation and tasting
ability and has prompted hypotheses as to the possible
relevance of bitter tasting for ultimate diet choice and
related health [13-15]. We note that the human genome
project has now identified more than twenty genes for
bitter taste [16], likely to also associate with health effects.
Existing studies assessing relationships between TAS2R38
haplotype variation and specific bitter tasting ability have
limited samples sizes and have largely been restricted to
the assessment of relationships between genetic variation
at the TAS2R38 locus and the binary measure
"taster/nontaster". Whilst there is evidence as to the existence of this
association, there has not to date, been large-scale
replication or refinement of these observations. Furthermore,
whilst diplotypes of the TAS2R38 gene locus are thought
to prescribe one's ability to detect the bitter compounds
PROP and PTC (PROP representing a suboptimal, but
effective ligand for the TAS2R38 receptor), little its known
about the effects/association of haplotypes at
intermediate/lower frequency or the cause of the distribution of
bitter tasting ability within haplotype defined groups.
Studies into the ps (...truncated)