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ADAM33 Gene Polymorphisms are Associated with the Risk of Idiopathic Pulmonary Fibrosis

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Abstract

Background

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea and worsening lung function due to remodeling of the lung, including epithelial mesenchymal transition. ADAM33 is a disintegrin and metalloprotease domain-containing protein, which may be related to lung fibrosis by exerting angiogenesis and remodeling of the lung. Thus, we evaluated the association of single-nucleotide polymorphisms (SNPs) of ADAM33 with the risk of IPF.

Methods

A total of 237 patients with IPF and 183 healthy subjects participated in the present study. Nine polymorphisms were selected. Genotyping was performed by single-base extension. Polymorphisms and haplotypes were analyzed for associations with the risk of IPF using multiple logistic regression models controlling for age, gender, and smoking status as covariates.

Results

All SNPs were in Hardy-Weinberg equilibrium. The minor allele frequency (MAF) of rs628977G>A in intron 21 was significantly lower in subjects with surgical IPF than in normal controls in the recessive model [33.2 vs. 38.0 %, p = 0.02, OR = 0.40 (0.19–0.84)]. When the subjects with clinical IPF were included, the difference in MAF persisted with a p value of 0.03 [OR = 0.50 (0.27–0.94)].

Conclusions

ADAM33 rs628977G>A was marginally associated with a decreased risk of IPF in a recessive model.

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Acknowledgments

The DNA samples were generously provided by the Soonchunhyang University, Bucheon Hospital Biobank, a member of the National Biobank of Korea, supported by the Ministry of Health, Welfare, and Family Affairs, Republic of Korea. This study was supported by grants of Ministry of Health & Welfare, Republic of Korea (A 010249 and A090548).

Conflict of interest

None to declare.

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Authors and Affiliations

  1. Division of Allergy and Respiratory Medicine, Soonchunhyang University Hospital, 657, Hannam-Dong, Yongsan-Gu, Seoul, 140-743, South Korea

    Soo-Taek Uh

  2. Genome Research Center for Allergy and Respiratory Disease, Soonchunhyang University Bucheon Hospital, 1174, Jung-Dong, Wonmi-Gu, Bucheon, Gyeonggi-Do, 420-020, South Korea

    An-Soo Jang, Sung-Woo Park, Jong-Sook Park, Chang-Gi Min & Choon-Sik Park

  3. Division of Respiratory Medicine, Soonchunhyang University, Chunan Hospital, Chunan, South Korea

    Yong Hoon Kim

  4. Department of Genetic Epidemiology, SNP-Genetics Inc., B-147, WooLim Lion’s Valley 317-28, Gasan-Dong, Geumcheon-ku, Seoul, 1530803, South Korea

    Byung-Lae Park & Hyoung Doo Shin

  5. Department of Life Science, Sogang University, Sinsu-dong, Mapo-gu, Seoul, 121-742, South Korea

    Hyoung Doo Shin

  6. Division of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan, Asanbyungwon-gil, Songpa-gu, Seoul, 138-736, South Korea

    Dong Soon Kim

  7. Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 1174, Jung-Dong, Wonmi-Ku, Bucheon, Kyeonggi-Do, 420-020, South Korea

    Choon-Sik Park

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  1. Soo-Taek Uh
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Correspondence to Choon-Sik Park.

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Uh, ST., Jang, AS., Park, SW. et al. ADAM33 Gene Polymorphisms are Associated with the Risk of Idiopathic Pulmonary Fibrosis. Lung 192, 525–532 (2014). https://doi.org/10.1007/s00408-014-9578-5

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  • DOI: https://doi.org/10.1007/s00408-014-9578-5

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