PTEN identified as important risk factor of chronic obstructive pulmonary disease

Hosgood, H. Dean; Menashe, Idan; He, Xingzhou; Chanock, Stephen; Lan, Qing

doi:10.1016/j.rmed.2009.06.016

« Previous Next »Respiratory Medicine
Volume 103, Issue 12 , Pages 1866-1870, December 2009

PTEN identified as important risk factor of chronic obstructive pulmonary disease

H. Dean Hosgood III
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA
- Corresponding author. National Cancer Institute, Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology Branch, 6120 Executive Boulelvard, EPS 8118, MCS 7240, Bethesda, MD 20892-7240, USA. Tel.: +1 301 594 4649; fax: +1 301 402 1819.
Idan Menashe
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA
Xingzhou He
- Chinese Center for Disease Control and Prevention, Beijing, PR China
Stephen Chanock
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA
Qing Lan
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA

Received 17 March 2009; accepted 25 June 2009. published online 22 July 2009.

Summary

Common genetic variation may play an important role in altering chronic obstructive pulmonary disease (COPD) risk. In Xuanwei, China, the COPD rate is more than twice the Chinese national average, and COPD is strongly associated with in-home coal use. To identify genetic variation that may be associated with COPD in a population with substantial in-home coal smoke exposures, we evaluated 1261 single nucleotide polymorphisms (SNPs) in 380 candidate genes potentially relevant for cancer and other human diseases in a population-based case–control study in Xuanwei (53 cases; 107 controls). PTEN was the most significantly associated gene with COPD in a minP analysis using 20,000 permutations (P=0.00005). SNP-based analyses found that homozygote variant carriers of PTEN rs701848 (OR_TT=0.12, 95% CI=0.03–0.47) had a significant decreased risk of COPD. PTEN, or phosphatase and tensin homolog, is an important regulator of cell cycle progression and cellular survival via the AKT signaling pathway. Our exploratory analysis suggests that genetic variation in PTEN may be an important risk factor of COPD in Xuanwei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuanwei and other populations with coal smoke exposures.