苦味受体基因（TAS2R38）、6-正丙基硫氧嘧啶（PROP）苦味与酒精摄入量
Bitter receptor gene (TAS2R38), 6-n-propylthiouracil (PROP) bitterness and alcohol intake.
作者信息
Duffy Valerie B, Davidson Andrew C, Kidd Judith R, Kidd Kenneth K, Speed William C, Pakstis Andrew J, Reed Danielle R, Snyder Derek J, Bartoshuk Linda M
机构信息
School of Allied Health, University of Connecticut, 358 Mansfield Rd., Box U-101, Storrs, CT 06269-2101, USA.
出版信息
Alcohol Clin Exp Res. 2004 Nov;28(11):1629-37. doi: 10.1097/01.alc.0000145789.55183.d4.
BACKGROUND
Phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP), chemically related compounds, are probes for genetic variation in bitter taste, although PROP is safer with less sulfurous odor. Threshold for PROP distinguishes nontasters (increased threshold) from tasters (lower threshold); perceived intensity subdivides tasters into medium tasters (PROP is bitter) and supertasters (PROP is very bitter). Compared with supertasters, nontasters have fewer taste papillae on the anterior tongue (fungiform papillae) and experience less negative (e.g., bitterness) and more positive (eg, sweetness) sensations from alcohol. We determined whether the TAS2R38 gene at 7q36 predicted PROP bitterness, alcohol sensation and use.
METHODS
Healthy adults (53 women, 31 men; mean age 36 years)--primarily light and moderate drinkers--reported the bitterness of five PROP concentrations (0.032-3.2 mM) and intensity of 50% ethanol on the general Labeled Magnitude Scale. PROP threshold and density of fungiform papillae were also measured. Subjects had common TAS2R38 gene haplotypes [alanine-valine-isoleucine (AVI) and proline-alanine-valine (PAV)].
RESULTS
PROP bitterness varied significantly across genotypes with repeated measures ANOVA: 26 AVI/AVI homozygotes tasted less bitterness than either 37 PAV/AVI heterozygotes or 21 PAV/PAV homozygotes. The PAV/PAV group exceeded the PAV/AVI group for bitterness only for the top PROP concentrations. The elevated bitterness was musch less than if we defined the groups using psychophysical criteria. With multiple regression analyses, greater bitterness from 3.2 mM PROP was a significant predictor of greater ethanol intensity and less alcohol intake--effects separate from age and sex. Genotype was a significant predictor of alcohol intake, but not ethanol intensity. With ANOVA, AVI/AVI homozygotes reported higher alcohol use than either PAV/AVI heterozygotes or PAV/PAV homozygotes. When age effects were minimized, PROP bitterness explained more variance in alcohol intake than did the TAS2R38 genotype.
CONCLUSIONS
These results support taste genetic effects on alcohol intake. PROP bitterness serves as a marker of these effects.
背景
苯硫脲（PTC）和6 - 正丙基硫氧嘧啶（PROP）是化学相关的化合物，是苦味味觉基因变异的探针，尽管PROP更安全，硫臭味较小。PROP阈值可区分非尝味者（阈值升高）和尝味者（阈值较低）；感知强度将尝味者细分为中等尝味者（PROP有苦味）和超级尝味者（PROP非常苦）。与超级尝味者相比，非尝味者在前舌（菌状乳头）上的味觉乳头较少，从酒精中体验到的负面（如苦味）感觉较少，正面（如甜味）感觉较多。我们确定了位于7q36的TAS2R38基因是否能预测PROP苦味、酒精感觉及饮酒情况。
方法
健康成年人（53名女性，31名男性；平均年龄36岁）——主要是轻度和中度饮酒者——用通用的标记量级量表报告了五种PROP浓度（0.032 - 3.2 mM）的苦味以及50%乙醇的强度。还测量了PROP阈值和菌状乳头密度。受试者具有常见的TAS2R38基因单倍型[丙氨酸 - 缬氨酸 - 异亮氨酸（AVI）和脯氨酸 - 丙氨酸 - 缬氨酸（PAV）]。
结果
通过重复测量方差分析，PROP苦味在不同基因型间有显著差异：26名AVI/AVI纯合子尝到的苦味比37名PAV/AVI杂合子或21名PAV/PAV纯合子中的任何一组都少。仅在最高PROP浓度时，PAV/PAV组的苦味超过PAV/AVI组。与我们使用心理物理学标准定义组相比，这种升高的苦味要小得多。通过多元回归分析，3.2 mM PROP带来的更强苦味是更高乙醇强度和更少酒精摄入量的显著预测因素——这些效应独立于年龄和性别。基因型是酒精摄入量的显著预测因素，但不是乙醇强度的预测因素。通过方差分析，AVI/AVI纯合子报告的饮酒量高于PAV/AVI杂合子或PAV/PAV纯合子。当年龄效应最小化时，PROP苦味比TAS2R38基因型能解释更多酒精摄入量的方差。
结论
这些结果支持味觉基因对酒精摄入量的影响。PROP苦味是这些影响的一个标志。
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