Genetic associations with hypoxemia and pulmonary arterial pressure in COPD.
BACKGROUND
Hypoxemia, hypercarbia, and pulmonary arterial hypertension are known complications of advanced COPD. We sought to identify genetic polymorphisms associated with these traits in a population of patients with severe COPD from the National Emphysema Treatment Trial (NETT).


METHODS
In 389 participants from the NETT Genetics Ancillary Study, single-nucleotide polymorphisms (SNPs) were genotyped in five candidate genes previously associated with COPD susceptibility (EPHX1, SERPINE2, SFTPB, TGFB1, and GSTP1). Linear regression models were used to test for associations among these SNPs and three quantitative COPD-related traits (Pao(2), Paco(2), and pulmonary artery systolic pressure). Genes associated with hypoxemia were tested for replication in probands from the Boston Early-Onset COPD Study.


RESULTS
In the NETT Genetics Ancillary Study population, SNPs in microsomal epoxide hydrolase (EPHX1) [p = 0.01 to 0.04] and serpin peptidase inhibitor, clade E, member 2 (SERPINE2) [p = 0.04 to 0.008] were associated with hypoxemia. One SNP within surfactant protein B (SFTPB) was associated with pulmonary artery systolic pressure (p = 0.01). In probands from the Boston Early-Onset COPD Study, SNPs in EPHX1 and in SERPINE2 were associated with the requirement for supplemental oxygen.


CONCLUSIONS
In participants with severe COPD, SNPs in EPHX1 and SERPINE2 were associated with hypoxemia in two separate study populations, and SNPs from SFTPB were associated with pulmonary artery pressure in the NETT participants.
Castaldi
Peter J
PJ
Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA.
Hersh
Craig P
CP
Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Electronic address: craig.hersh@channing.harvard.edu.
Reilly
John J
JJ
Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Silverman
Edwin K
EK
Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
D000368:Aged; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D006801:Humans; D006935:Hypercapnia / Q000150:complications / Q000235:genetics; D006976:Hypertension, Pulmonary / Q000150:complications / Q000235:genetics*; D000860:Hypoxia / Q000150:complications / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D058255:Protease Nexins; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000235:genetics*; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D058258:Serpin E2
D016564:Amyloid beta-Protein Precursor; D058255:Protease Nexins; D037701:Pulmonary Surfactant-Associated Protein B; D011956:Receptors, Cell Surface; C545486:SERPINE2 protein, human; D058258:Serpin E2; D004851:Epoxide Hydrolases