Abstract
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 (FEV1)% predicted and three SNPs (rs16969968, rs8034191 and rs1051730) in CHRNA3/5 were both associated with FEV1% predicted and FEV1/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.
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Acknowledgements
We want to thank Binmiao Liang, Hong Cheng, Jia Deng for their work on the specimen collection. This study was supported by the National Natural Science Foundation of China grants 8107003, and 31071009.
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Zhou, H., Yang, J., Li, D. et al. Association of IREB2 and CHRNA3/5 polymorphisms with COPD and COPD-related phenotypes in a Chinese Han population. J Hum Genet 57, 738–746 (2012). https://doi.org/10.1038/jhg.2012.104
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DOI: https://doi.org/10.1038/jhg.2012.104
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