Association of IREB2 and CHRNA3/5 polymorphisms with COPD and COPD-related phenotypes in a Chinese Han population.
Genome-wide association studies and integrative genomics approaches have demonstrated significant associations between chronic obstructive pulmonary disease (COPD) and single-nucleotide polymorphisms (SNPs) in the chromosome 15q25 region that includes iron-responsive element binding protein 2 gene (IREB2) and CHRNA3/5 in non-Asian populations. We investigated whether IREB2 and CHRNA3/5 polymorphisms would be associated with COPD susceptibility and COPD-related phenotypes in a Chinese Han population. Eight SNPs (rs2568494, rs2656069, rs10851906, rs1964678, rs12593229, rs965604, rs13180, rs17483929) in IREB2 gene and four SNPs (rs16969968, rs1051730, rs938682, rs8034191) in or near CHRNA3/5 locus were genotyped in a case-control study (680 COPD patients and 687 controls). No significant associations were found between any of the SNPs and COPD in either former-smokers or current-smokers. Two SNPs (rs2656069 and rs10851906) in IREB2 were associated with COPD (P=0.045 and 0.032, respectively) in non-smoker. Four SNPs (rs1964678, rs12593229, rs965604 and rs13180) in IREB2 were associated with forced expiratory volume in 1 s (FEV(1))% predicted and three SNPs (rs16969968, rs8034191 and rs1051730) in CHRNA3/5 were both associated with FEV(1)% predicted and FEV(1)/FVC in COPD cases (P range 0.007-0.050). The SNP rs8034191 near CHRNA3/5 locus was significantly associated with pack-years of smoking in COPD patients (P=0.033). We demonstrated IREB2 polymorphisms were associated with COPD in non-smoking subjects, and the effect of IREB2 gene on COPD may be independent from smoking and independent from CHRNA3/5 gene cluster. Besides, we confirmed that SNPs in these two gene loci were associated with pulmonary function and CHRNA3/5 polymorphism was associated with pack-year of smoking in COPD patients in the Chinese Han population.
Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
Haixia
H
Zhou
Jing
J
Yang
Dengxue
D
Li
Jun
J
Xiao
Bo
B
Wang
Lan
L
Wang
Chunlan
C
Ma
Sicheng
S
Xu
Xuemei
X
Ou
Yulin
Y
Feng
D000368:Aged; D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D016022:Case-Control Studies; D002681:China; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D035942:Iron Regulatory Protein 2 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008168:Lung / Q000502:physiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000235:genetics
D035942:Iron Regulatory Protein 2; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human