Associations between taste genetics, oral sensation and alcohol intake
Introduction
Numerous studies support a familial component in the etiology of alcoholism (see Ref. [1] for review). A study of more than 3500 male twins in the United States [2] suggests both direct and indirect mechanisms in the heritability of alcoholism. Although direct mechanisms could include specific gene loci that control alcohol metabolism (e.g., alcohol dehydrogenase [3]), they are more likely to involve multiple chromosomes [4]. Indirect mechanisms include comorbid conditions, such as affective and conduct disorders [5] as well as personality disorders [6]. One direct mechanism could involve genetic variation in taste and oral sensation. This paper explores associations between genetic variation in taste, oral responses to an alcohol probe and consumption of alcoholic beverages.
Bitterness of phenylthiocarbamide (PTC) or the chemically related compound, 6-n-propylthiouracil (PROP), provides a phenotypic marker for genetic variation in taste and oral sensation. Historically, researchers have used detection thresholds to classify individuals as nontasters or tasters of these bitter compounds (e.g., [7], [8]). Family studies have shown that individuals who are nontasters have two recessive alleles, while tasters may carry one or both dominant alleles [9], [10]. Insensitivity to PTC or PROP is estimated at 30% of the Caucasian population; the percentages vary with sex and race [11].
Scaling the intensity of PROP bitterness allows separation of tasters into “medium tasters” (those who taste PROP as bitter) and “supertasters” (those who taste PROP as exceptionally bitter) [12]. Supertasters cannot be identified via thresholds [13] and thus, effects due to supertasters cannot be revealed in studies classifying subjects by PROP threshold only. Responses to PTC/PROP associate with allelic variation on chromosome 5 [14] and 7 [14], [15], regions that contain genes for putative bitter receptors (e.g., [16], [17]). Single nucleotide polymorphisms in putative bitter receptors TAS2R3, TAS2R4 and TAS2R5 do not explain variation in PROP bitterness [18]. Supertasting may result from increased density of fungiform papilla as well as allelic variation that results in the presence or absence of a specific PROP receptor as proposed [19] and supported by preliminary data [20].
PROP bitterness influences oral sensations from alcohol, a relationship that appears to be mediated through fungiform papilla. Greater PROP bitterness associates with more bitterness from ethanol [21] and some types of beer [22], more bitterness, astringency and acidity from red wines [23], and greater irritation from ethanol [21], [24]. A PROP bitterness and fungiform papilla relationship was first shown by Miller and Reedy [25]; PROP supertasters have, on average, the greatest number of fungiform papillae and taste buds as assessed with videomicroscopy [11]. A positive relationship between PROP bitterness and fungiform papillae number is also observed using lower magnification for papillae counting [26], [27]. Fungiform papillae hold taste buds that are innervated for taste by the chorda tympani branch (CTN) of the facial nerve (cranial nerve VII). These taste buds are surrounded by fibers of the trigeminal nerve (cranial nerve V), which are believed to mediate oral burn [28], [29], [30].
Oral sensory differences in alcohol sensation with PROP tasting may explain some of the variability in alcohol preference and drinking behaviors [31]. Nontasters of PROP may experience the least bitterness/oral burn from alcohol and thus have greater preference for and consumption of alcoholic beverages. By scaling PROP bitterness, Intranuovo and Powers [22] found that those who tasted PROP as least bitter consumed significantly more beers in their first year of drinking. Guinard et al. [32] also reported that high users of beer (greater than 3.6 L per week) were more likely to be PTC/PROP nontasters than were low users (less than 720 ml per week). However, the method for PROP and PTC was described as a screening procedure without clear indication of how nontasters were defined. Mattes and DiMeglio [33] did not find differences in intake of alcoholic beverages between PTC tasters and nontasters. In this study, subjects tasted filter papers without PTC and those saturated with PTC. Nontasters were those who reported both papers as tasteless; tasters were those who rated the PTC-saturated paper as bitter. Differences in psychophysical methodologies used to define PROP/PTC may explain some differences across these studies (see discussion below).
There is inconsistent support for PROP as a genetic marker for risk of alcoholism. In studies with alcoholics compared with controls, some report an excess of nontasters among the alcoholics [34], [35], [36] while other studies do not [37], [38], [39]. DiCarlo and Powers [36] also found a higher proportion of PROP supertasters in college students who reported both problems with alcoholism and depression in themselves and their parents than in nontasters. In studies examining family history of alcoholism, Pelchat and Danowski [31] found significantly more PROP nontasters among children of alcoholics than among children of nonalcoholics, whether or not the children themselves were alcoholic. Kranzler et al. [40] did not find a significant relationship between PROP threshold and parental history of alcohol dependence in nonalcoholic young adults or in those with alcohol dependency [41].
Some of the inconsistencies in PROP effects on alcohol consumption behaviors could relate to the measurement of PROP tasting. Some of the studies that fail to find a PROP–alcohol association have methodological problems as reviewed by Pelchat and Danowski [31], including inappropriate matches between alcoholics and controls [39] and procedures that may falsely classify nontasters through a “yes/no” response to a PTC-impregnated paper [37] or a single PTC solution [38]. Studies on alcohol ingestive behaviors that use a threshold procedure [31], [34], [35], [40], [41] will fail to reveal PROP effects if the behavioral differences are most apparent across those who vary most in PROP tasting (i.e., nontasters and supertasters). DiCarlo and Powers [36] used the bitterness of the PROP-impregnated paper [42] to examine PROP effects on alcohol ingestive behaviors. Subjects were defined as nontasters, medium tasters and supertasters based on their ratings of bitterness of PROP using a nine-point category scale. Methodological advances show that these category scales may not accurately classify supertasting [13], [43]. Characterization of supertasters and related sensory behaviors requires scaling methods that permit valid comparisons across subjects. The methodological difficulties in identifying supertasting has been reviewed previously [13], [43] and will be reviewed here briefly.
Adjective-labeled, self-rating scales (e.g., Likert, category and visual analogue) are commonly used in taste studies. They are valid for within-subject comparisons; however, they are invalid for across-subject/group comparisons unless the adjectives denote the same perceived intensity, on average, to all groups of interest. However, intensity adjectives denote different absolute perceived intensities within subjects, depending on the domain to which they are applied. For example, a “strong” oral burn from a chili pepper reflects a greater perceived intensity than a “strong” rose odor. Intensity adjectives also denote different absolute perceived intensities across subjects depending on the subject's experience with the domain of interest. For taste, supertasters experience greater perceived intensities than do nontasters (see [13], [43], [44] for reviews); thus, a “strong” bitter to a supertaster is more intense than a “strong” bitter to a nontaster. Using adjective-labeled scales to make across-group comparisons when the groups, on average, use the adjectives to refer to different perceived oral sensory intensities obviously invalidates the comparisons [45]. Most of the time, the invalid comparison will simply underrepresent the actual effect size (e.g., Ref. [46]). However, in some cases, the invalid comparison will produce apparent differences that are actually in the wrong direction (see Ref. [45] for a review). For example, suppose that the adjective “strong” reflects a perceived intensity that is twice as great to supertasters as it is to nontasters. Suppose an alcoholic beverage were 10% more intense to supertasters. Treating “strong” as if it reflected the same perceived intensity to both groups effectively reduces all of the supertaster ratings by half. Thus, a beverage that is 10% more intense would be reduced so far that the reduced rating for supertasters would fall below that for nontasters. We call this a reversal artifact.
Environmental factors, which impact oral sensation, affect the study of taste genetic influences on alcohol ingestive behaviors [42]. Depressed taste from the cranial nerves can alter oral sensations by changing the interactions among taste nerves [47], between taste nerves and trigeminal nerves [48] and possibly between taste and retronasal olfaction [49]. For example, an individual with depressed CTN taste relative to density of fungiform papillae or PROP taster status may have altered taste and somatosensory sensations that appear as phantom taste or pain sensations [50] or intensified taste and somatosensory sensations in response to oral stimuli [48], [51]. Otherwise healthy adults can show depressed CTN taste relative to whole mouth sensations because of common illnesses, such as otitis media, middle-ear infection [42]. The logic of these findings is that damage to the CTN releases the usual inhibition from other nerves to intensify oral sensations. In relation to taste and alcohol, some studies have reported that individuals with a paternal history of alcoholism rated greatest intensity to concentrated sodium chloride (NaCl) and citric acid [52], [53]. If these individuals were more likely nontasters, following the taste genetic hypothesis, those with the paternal history should have lowest intensity ratings of NaCl and citric acid (e.g., [44], [54], [55]). The question remains if these opposing findings result from interactions between genetic taste and environmental influences, which affect oral sensations and alcohol ingestive behaviors. Intensification of NaCl intensity has been seen in aged versus young women and the intensification is thought to result from increased trigeminal sensations as the result of taste damage [51].
The primary goal of the present study was to examine relationships between markers of taste genetics (perceived bitterness of PROP, PROP threshold and fungiform papilla number) and sensory responses to ethyl alcohol as well as reported intake of alcoholic beverages in adults. Existing data afforded analysis of relationships between the alcohol variables, NaCl and citric acid intensity, and a measure of CTN taste functioning. Multiple regression analyses were used to determine the ability of taste genetic and other taste markers to predict alcohol variables.
For intensity and hedonic ratings, subjects used the general Labeled Magnitude Scale (gLMS) [43], [45], which is a generalization of the adjective-labeled, ratio scale devised by Green et al. [56], [57]. The important change concerns the label at the top of the scale: “strongest imaginable sensation of any kind.” The idea behind the choice of this label was to “stretch” the adjective-labeled scale to its maximum. To the extent that this maximal experience is equivalent across subjects, the gLMS will act as a universal sensory ruler. Even if this is not the case, this maximal experience is unlikely to be associated with taste. This means that the gLMS should produce valid comparisons, on average, across nontasters, medium tasters and supertasters of PROP. Previous research has shown that PROP taste functions for nontasters, medium tasters and supertasters produced by the gLMS are equivalent to those obtained by magnitude matching [13], [58].
Section snippets
Subjects and procedure
Subjects participated in an observational study designed to examine the relationship between genetic variation in taste and food/beverage sensations, dietary behaviors and nutritional status in adults. The goal of subject recruitment was to obtain diversity in genetic variation in taste in males and females and to minimize confounding factors that would affect the ability to examine taste genetic influences on dietary behaviors.
A telephone screening and the first visit served to recruit healthy
Results
The sample had diversity in PROP tasting and fungiform papilla number. PROP threshold scores ranged from 0.0015 to 2.18 mM and had the usual bimodal distribution (Fig. 1). Fig. 2 shows PROP functions for subjects divided by bitterness of 3.2 mM PROP into 20 subjects who tasted PROP as less than moderate (≤22 on the gLMS), 38 who tasted PROP between moderate and very strong (>22 to 53 on the gLMS), and 25 who tasted PROP as very strong or greater (>53 on the gLMS); the normalized ratings
Discussion
This study of healthy adults showed significant associations between oral sensation and intake of alcoholic beverages. Those who tasted the least bitterness from concentrated PROP or had lowest numbers of fungiform papilla, as markers for genetic nontasters, reported less burn and disliking of a 50% alcohol probe painted on the tongue tip as well as more frequent consumption of alcoholic beverages. The spatial pattern of oral sensation also explained variation in burn from the alcohol probe and
Acknowledgements
This research was presented at the 2000 Annual Meeting of the Association for Chemoreception Sciences [80] and was supported by 2002-00788 NRICGP/USDA (V. Duffy), The University of Connecticut Research Foundation (V. Duffy) and NIH DC00283 (L. Bartoshuk).
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