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.
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.
Takabatake
Noriaki
N
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2, Iida-Nishi, Yamagata 990-9585, Japan. ntakabatake@tohoku-ctr-hsp.com
Toriyama
Sayumi
S
Takeishi
Yasuchika
Y
Shibata
Yoko
Y
Konta
Tsuneo
T
Inoue
Sumito
S
Abe
Shuichi
S
Igarashi
Akira
A
Tokairin
Yoshikane
Y
Ishii
Miho
M
Koyano
Satoru
S
Emi
Mitsuru
M
Kato
Takeo
T
Kawata
Sumio
S
Kubota
Isao
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D018035:Receptors, Odorant / Q000235:genetics*; D012129:Respiratory Function Tests / Q000706:statistics & numerical data*; D014797:Vital Capacity / Q000235:genetics*
D018035:Receptors, Odorant