title: PTEN identified as important risk factor of chronic obstructive pulmonary disease.
abstract: 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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
authors.forename: H Dean
authors.initials: HD
authors.lastname: Hosgood
authors.forename: Idan
authors.initials: I
authors.lastname: Menashe
authors.forename: Xingzhou
authors.initials: X
authors.lastname: He
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
mesh_terms: D016902:Air Pollution, Indoor / Q000009:adverse effects*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D003031:Coal; D004781:Environmental Exposure; D004812:Epidemiologic Methods; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000235:genetics*; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000453:epidemiology / Q000235:genetics
chemical_list: D003031:Coal; D012906:Smoke; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human