Genetic Variation in the Odorant Receptor OR2J3 Is Associated with the Ability to Detect the "Grassy" Smelling Odor, cis-3-hexen-1-ol
Genetic Variation in the Odorant Receptor OR2J3 Is Associated with the Ability to Detect the "Grassy" Smelling Odor, cis-3-hexen-1-ol
复制标题
DOI：
10.1093/chemse/bjs049
复制
发表时间：
2012-09-01
期刊：
影响因子：
3.5
通讯作者：
Newcomb, Richard D.
中科院分区：
文献类型：
--
作者：
McRae, Jeremy F.;Mainland, Joel D.;Newcomb, Richard D.
检测多种气味的能力因人而异；然而，已经针对相对较少的化合物评估了基因型对这种变异的贡献。我们已经确定了检测风味化合物 cis-3-hexen-1-ol 能力的遗传基础。这种化合物通常被描述为“青草味”或“割草的气味”，其检测能力的变化与人类 6 号染色体上包含 25 个气味受体基因的区域中的单核苷酸多态性 (SNP) 有关。我们对 52 个种族混合群体中所有 25 个受体的编码区进行了测序，并鉴定了 147 个序列变异。我们测试了这些与 cis-3-hexen-1-ol 检测阈值的关联，发现了 3 个密切相关的 SNP，其中包括在功能性气味受体中发现的一个（OR2J3 中的 rs28757581）。对来自该地区的 13 种气味受体进行的体外测定确定了 3 种可以响应 cis-3-hexen-1-ol 的受体，其中包括 OR2J3。该基因包含 52 个个体的 5 个预测单倍型。我们在体外测试了所有 5 个单倍型以及它们自己的几个氨基酸取代，例如 rs28757581 (T113A)。两个氨基酸取代 T113A 和 R226Q 损害了 OR2J3 响应 cis-3-hexen-1-ol 的能力，并且这两个取代一起有效地消除了对该化合物的响应。包含 T113A 和 R226Q 的 OR2J3 单倍型解释了我们研究队列中 cis-3-hexen-1-ol 检测变异的 26.4%。需要进一步的研究来检验 OR2J3 单倍型是否可以解释感知风味体验的变化以及含有 cis-3-hexen-1-ol 的食物的消费。
The ability to detect many odors varies among individuals; however, the contribution of genotype to this variation has been assessed for relatively few compounds. We have identified a genetic basis for the ability to detect the flavor compound cis-3-hexen-1-ol. This compound is typically described as "green grassy" or the smell of "cut grass," with variation in the ability to detect it linked to single nucleotide polymorphisms (SNPs) in a region on human chromosome 6 containing 25 odorant receptor genes. We have sequenced the coding regions of all 25 receptors across an ethnically mixed population of 52 individuals and identified 147 sequence variants. We tested these for association with cis-3-hexen-1-ol detection thresholds and found 3 strongly associated SNPs, including one found in a functional odorant receptor (rs28757581 in OR2J3). In vitro assays of 13 odorant receptors from the region identified 3 receptors that could respond to cis-3-hexen-1-ol, including OR2J3. This gene contained 5 predicted haplotypes across the 52 individuals. We tested all 5 haplotypes in vitro and several amino acid substitutions on their own, such as rs28757581 (T113A). Two amino acid substitutions, T113A and R226Q, impaired the ability of OR2J3 to respond to cis-3-hexen-1-ol, and together these two substitutions effectively abolished the response to the compound. The haplotype of OR2J3 containing both T113A and R226Q explains 26.4% of the variation in cis-3-hexen-1-ol detection in our study cohort. Further research is required to examine whether OR2J3 haplotypes explain variation in perceived flavor experience and the consumption of foods containing cis-3-hexen-1-ol.