A nonfunctioning single nucleotide polymorphism in olfactory receptor gene family is associated with the forced expiratory volume in the first second/the forced vital capacity values of pulmonary function test in a Japanese population.
A nonfunctioning single nucleotide polymorphism in olfactory receptor gene family is associated with the forced expiratory volume in the first second/the forced vital capacity values of pulmonary function test in a Japanese population.
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DOI：
10.1016/j.bbrc.2007.10.068
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发表时间：
2007-12
影响因子：
3.1
通讯作者：
N. Takabatake;S. Toriyama;Y. Takeishi;Y. Shibata;T. Konta;S. Inoue;S. Abe;A. Igarashi;Yoshikane Tokairin;M. Ishii;Satoru Koyano;M. Emi;T. Kato;S. Kawata;I. Kubota
中科院分区：
文献类型：
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作者：
N. Takabatake;S. Toriyama;Y. Takeishi;Y. Shibata;T. Konta;S. Inoue;S. Abe;A. Igarashi;Yoshikane Tokairin;M. Ishii;Satoru Koyano;M. Emi;T. Kato;S. Kawata;I. Kubota
第一秒用力呼气量（FEV1.0）/用力肺活量（FVC）是单次用力呼气的重要指标。人嗅觉受体（OR）基因家族在肺中的异位表达表明其可能参与呼吸生理。我们假设FEV1.0/FVC值的个体差异可能归因于OR基因家族的遗传变异，这些遗传变异是由无功能的SNPs（nSNPs）引起的。我们通过方差分析对山形高勋队列的2970个样本中具有7个OR基因nSNP的人群和FEV1.0/FVC值进行了数量性状位点（QTL）分析。我们发现一个nSNP [rs 10838851，OR，family 4，subfamily X，member 1（OR 4X 1）gene，Tyr 273 Ter R2]与FEV1.0/FVC（%）显著相关（P=0.008）。OR 4X 1基因nSNP Ter/Ter、Ter/Tyr和Tyr/Tyr的FEV1.0/FVC值（%）分别为78.9±0.2、78.2±0.2和77.7±0.4。基于单倍型的OR 4X 1基因与FEV1.0/FVC值的分析表明，两种独特的单倍型[Hap-1/Hap-2（频率0.669/0.330）：SNP1（rs7106648）T/A-SNP2（rs871249）G/A-SNP3（rs713325）G/A-SNP4（rs 10838851）A（Tyr）/T（Tyr）-SNP 5（rs 4752923）G/A-SNP 6（rs 960640）G/A]与FEV1.0/FVC值显著相关（总体P=0.005）。提示OR 4X 1基因可能是肺功能测定中FEV1.0/FVC值个体差异的重要基因之一。
The forced expiratory volume in the first second (FEV1.0)/the forced vital capacity (FVC) is an important index of a single forced expiration. Ectopic expression of the human olfactory receptor (OR) gene family in the lungs has suggested its potential involvement of respiratory physiology. We hypothesized that the individual variability of FEV1.0/FVC value may be attributed to the genetic variance of the OR gene family caused by the nonfunctioning SNPs (nSNPs). We conducted quantitative trait locus (QTL) analyses of population having the 7 OR gene nSNPs and FEV1.0/FVC values by ANOVA, in 2970 samples in the Yamagata Takahata cohort. We found significant association of one nSNP [rs10838851, OR, family 4, subfamily X, member 1 (OR4X1) gene, Tyr273Ter∗] with FEV1.0/FVC (%) (P=0.008). The FEV1.0/FVC value (%) of population having OR4X1 gene nSNP Ter∗/Ter∗, Ter∗/Tyr, and Tyr/Tyr were 78.9±0.2, 78.2±0.2, and 77.7±0.4, respectively. Haplotype-based analysis of the OR4X1 gene with FEV1.0/FVC values demonstrated that two exclusive haplotypes [Hap-1/Hap-2 (frequency 0.669/0.330): SNP1 (rs7106648)T/A-SNP2 (rs871249)G/A-SNP3 (rs713325)G/A-SNP4 (rs10838851)A (Ter∗)/T (Tyr)-SNP5 (rs4752923)G/A-SNP6 (rs960640)G/A] were significantly associated with FEV1.0/FVC values (global P=0.005). These results suggest that OR4X1 may be one of the genes that contribute to the individual variability of FEV1.0/FVC value in pulmonary function test.