[논문]Polymorphisms in PDE4D are Associated with a Risk of COPD in Non-Emphysematous Koreans

Yoon, Hyoung-Kyu; Hu, Hae-Jin; Rhee, Chin-Kook; Shin, Seung-Hoon; Oh, Yeon-Mok; Lee, Sang-Do; Jung, Seung-Hyun; Yim, Seon-Hee; Kim, Tae-Min; Chung, Yeun-Jun

doi:10.3109/15412555.2014.898045

Polymorphisms in PDE4D are Associated with a Risk of COPD in Non-Emphysematous Koreans 원문보기

COPD : Journal of Chronic Obstructive Pulmonary Disease, v.11 no.6, 2014년, pp.652 - 658

Yoon, Hyoung-Kyu (Division of Pulmonary Disease and Critical Care, Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea) , Hu, Hae-Jin (Integrated Research Centre for Genome Polymorphism, Department of Microbiology, Department of Medical Informatics, The Catholic University of Korea, College of Medicine, Seoul, Korea) , Rhee, Chin-Kook (Division of Pulmonary Disease and Critical Care, Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea) , Shin, Seung-Hoon (Integrated Research Centre for Genome Polymorphism, Department of Microbiology, Department of Medical Informatics, The Catholic University of Korea, College of Medicine, Seoul, Korea) , Oh, Yeon-Mok (Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea) , Lee, Sang-Do (Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Me) , Jung, Seung-Hyun , Yim, Seon-Hee , Kim, Tae-Min , Chung, Yeun-Jun

Abstract ▼ AI-Helper

Despite extensive effort, only a few chronic obstructive pulmonary disease (COPD)-associated genes have been suggested, indicating that there must be additional risk-associated loci. Here we aimed to identify additional COPD-associated SNPs and to explore the potential relationship between COPD subgroups and the SNPs in the Korean population. We performed a genome-wide association study (GWAS) with 990 Korean individuals; 102 COPD cases and 544 controls for GWAS using Affymetrix SNP array 5.0, and 173 COPD cases and 171 controls for replication. After validating the candidate single nucleotide polymorphisms (SNP), we performed subgroup analysis by disease phenotype. Through GWAS, we identified a novel SNP in the phosphodiesterase-4D (PDE4D) gene [rs16878037 (C>T), p = 1.66 ◊ 10−6] that was significantly associated with COPD. This signal in PDE4D was successfully replicated in the independent set (p = 0.041). When we combined the discovery and replication data, the association signal became more significant (p = 5.69 ◊ 10−7). In the COPD subgroup analysis, the T allele of rs16878037 was significantly more frequent in COPD patients without severe diffusion capacity impairment (mild mixed and obstruction-dominant group) than in patients with severe impairment (severe mixed and emphysema-dominant groups). This result supports that PDE4D polymorphisms might be involved in the susceptibility to COPD especially in non-emphysematous individuals and that they could also affect the responsiveness of the PDE4 inhibitor treatment.

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Polymorphisms in PDE4D are Associated with a Risk of COPD in Non-Emphysematous Koreans 원문보기

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Polymorphisms in PDE4D are Associated with a Risk of COPD in Non-Emphysematous Koreans 원문보기

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