Genetic, Functional, and Phenotypic Diversity in TAS2R38-Mediated Bitter Taste Perception
Genetic, Functional, and Phenotypic Diversity in TAS2R38-Mediated Bitter Taste Perception
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DOI：
10.1093/chemse/bjt016
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发表时间：
2013-07-01
期刊：
影响因子：
3.5
通讯作者：
Wooding, Stephen P.
中科院分区：
文献类型：
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作者：
Behrens, Maik;Gunn, Howard C.;Wooding, Stephen P.
TAS2R38苦味受体的突变多态性是分离化合物如苯硫脲（PTC）和丙硫尿嘧啶（PROP）阈值味觉检测的关键决定因素，也是复杂的味觉介导性状如饮食选择和吸烟习惯的关键决定因素。这些关系在一定程度上是由两个功能不同的常见等位基因TAS2R38-PAV和TAS2R38-AVI造成的。然而，TAS2R38含有广泛的额外多态性，其功能意义尚不清楚。为了研究这种变异，我们通过全基因测序确定了56名高加索人的遗传多样性，利用体外实验分析了等位基因对5种TAS2R38激动剂（PTC、PROP、甲状腺素、甲巯咪唑和紫荆素）的特异性反应，并评估了基因型与阈值检测表型的相关性。测序发现3个单核苷酸替换编码3个氨基酸变化（C145G/P49A、C785T/A262V和A886G/I296V），这些替换组合形成6个单倍型。体外实验显示，不同等位基因的反应范围是连续的，所有单核苷酸多态性（P < 0.002）和PAV/AVI单倍型（P < 0.001）与阈值的相关性都很显著。在我们的样本中，除了PAV和AVI之外的单倍型没有表现出表型关联，可能是由于它们的低频率。然而，先前的研究表明，这些等位基因在全球一些地区是常见的，这表明我们样本中罕见的等位基因可能在其他人群中具有表型相关性。
Mutational polymorphism in the TAS2R38 bitter taste receptor is a key determinant of threshold taste detection of isolated compounds, such as phenylthiocarbamide (PTC) and propylthiouracil (PROP), as well as complex orosensation-mediated traits such as diet choice and smoking habits. These relationships are accounted for, in part, by 2 common alleles differing in functionality, TAS2R38-PAV and TAS2R38-AVI. However, TAS2R38 harbors extensive additional polymorphism whose functional significance remains unknown. To examine this variation, we ascertained genetic diversity in 56 Caucasian subjects via whole-gene sequencing, analyzed allele-specific responses to 5 TAS2R38 agonists (PTC, PROP, goitrin, methimazole, and sinigrin) using in vitro assays, and assessed genotypic associations with threshold detection phenotypes. Sequencing identified 3 single-nucleotide substitutions encoding 3 amino acid changes (C145G/P49A, C785T/A262V, and A886G/I296V), which combined to form 6 haplotypes in our sample. In vitro assays revealed a continuous range of response across alleles, and associations with threshold were significant for all single nucleotide polymorphisms (P < 0.002) and PAV/AVI haplotypes (P < 0.001). Haplotypes other than PAV and AVI did not exhibit phenotypic associations in our sample, possibly as a result of their low frequencies. However, prior studies have indicated that these alleles are common in some global regions, suggesting that alleles rare in our sample may be phenotypically relevant in other populations.