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人类tas1r1、tas1r3和mGluR1中的非同义单核苷酸多态性与个体对谷氨酸的味觉敏感性

Nonsynonymous single nucleotide polymorphisms in human tas1r1, tas1r3, and mGluR1 and individual taste sensitivity to glutamate.

作者信息

Raliou Mariam, Wiencis Anna, Pillias Anne-Marie, Planchais Aurore, Eloit Corinne, Boucher Yves, Trotier Didier, Montmayeur Jean-Pierre, Faurion Annick

机构信息

NBS-NOPA, Institut National de la Recherche Agronomique, Jouy-en-Josas, France.

出版信息

Am J Clin Nutr. 2009 Sep;90(3):789S-799S. doi: 10.3945/ajcn.2009.27462P. Epub 2009 Jul 1.

Abstract

Several studies indicate an essential role of the heterodimer Tas1R1-Tas1R3 for monosodium l-glutamate (MSG) detection, although others suggest alternative receptors. Human subjects show different taste sensitivities to MSG, and some are unable to detect the presence of glutamate. Our objective was to study possible relations between phenotype (sensitivity to glutamate) and genotype (polymorphisms in candidate glutamate taste receptors tas1r1, tas1r3, mGluR4, and mGluR1) at the individual level. The sensitivity was measured with a battery of tests to distinguish the effect of sodium ions from the effect of glutamate ions in MSG. A total of 142 genetically unrelated white French subjects were categorized into 27 nontasters (specific ageusia), 21 hypotasters, and 94 tasters. Reverse transcriptase polymerase chain reaction and immunohistochemistry showed expression of tas1r1, tas1r3, and alpha-gustducin in fungiform papillae in all 12 subjects tested, including subjects who presented specific ageusia for glutamate. Amplification and sequencing of cDNA and genomic DNA allowed the identification of 10 nonsynonymous single nucleotide polymorphisms (nsSNPs) in tas1r1 (n = 3), tas1r3 (n = 3), and mGluR1 (n = 4). In our sample of subjects, the frequencies of 2 nsSNPs, C329T in tas1r1 and C2269T in tas1r3, were significantly higher in nontasters than expected, whereas G1114A in tas1r1 was more frequent in tasters. These nsSNPs along with minor variants and other nsSNPs in mGluR1, including T2977C, account for only part of the interindividual variance, which indicates that other factors, possibly including additional receptors, contribute to glutamate sensitivity.

摘要

多项研究表明,异二聚体Tas1R1-Tas1R3在检测l-谷氨酸钠(MSG)中起关键作用,不过也有其他研究提出了替代受体。人类受试者对MSG表现出不同的味觉敏感性,有些人无法察觉谷氨酸的存在。我们的目标是在个体水平上研究表型(对谷氨酸的敏感性)与基因型(候选谷氨酸味觉受体tas1r1、tas1r3、代谢型谷氨酸受体4(mGluR4)和代谢型谷氨酸受体1(mGluR1)中的多态性)之间的可能关系。通过一系列测试来测量敏感性,以区分MSG中钠离子和谷氨酸离子的作用。总共142名无亲缘关系的法国白人受试者被分为27名无味觉者(特定味觉缺失)、21名味觉减退者和94名味觉正常者。逆转录聚合酶链反应和免疫组织化学显示,在所有12名受试对象的菌状乳头中均有tas1r1、tas1r3和α-味导素的表达,包括对谷氨酸有特定味觉缺失的受试者。对cDNA和基因组DNA进行扩增和测序后,在tas1r1(n = 3)、tas1r3(n = 3)和mGluR1(n = 4)中鉴定出10个非同义单核苷酸多态性(nsSNP)。在我们的受试者样本中,tas1r1中的2个nsSNP(C329T)和tas1r3中的C2269T在无味觉者中的频率显著高于预期,而tas1r1中的G1114A在味觉正常者中更为常见。这些nsSNP以及mGluR1中的次要变体和其他nsSNP(包括T2977C)仅占个体间差异的一部分,这表明其他因素(可能包括其他受体)也会影响谷氨酸敏感性。

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