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Genetic influences on right ventricular systolic pressure (RVSP) in chronic obstructive pulmonary disease (COPD)

DOI: 10.1186/1471-2466-12-25

Keywords: COPD, Pulmonary hypertension, Genetic polymorphism

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In patients with COPD, we genotyped 7 SNPs in 6 candidate PH genes (NOS3, ACE, EDN1, PTGIS, SLC6A4, VEGFA). We tested for association with right ventricular systolic pressure (RVSP), spirometry and gas transfer, and hypoxemia.580 COPD patients were recruited, 341 patients had a transthoracic echocardiogram, with RVSP measurable in 278 patients (mean age 69?years, mean FEV1 50% predicted, mean RVSP 44?mmHg, median history of 50 pack-years). Of the 7 tested SNPs, the NOS3-VNTR polymorphism was significantly associated with RVSP in a dose-dependent fashion for the risk allele: mean RVSP for a/a and a/b genotypes were 52.0 and 46.6?mmHg respectively, compared to 43.2?mmHg for b/b genotypes (P?=?0.032). No associations were found between RVSP and other polymorphisms. ACE II or ID genotypes were associated with a lower FEV1% predicted than the ACE DD genotype (P?=?0.028). The NOS3-298 TT genotype was associated with lower KCO % predicted than the NOS3-298 GG or GT genotype (P?=?0.031).The NOS3-VNTR polymorphism was associated with RVSP in patients with COPD, supporting its involvement in the pathogenesis of PH in COPD. ACE and NOS3 genotypes were associated with COPD disease severity, but not with the presence of PH. Further study of these genes could lead to the development of prognostic and screening tools for PH in COPD.Pulmonary hypertension (PH) is a serious complication of chronic obstructive pulmonary disease (COPD) and develops in 30% to 70% of patients with COPD, increasing their morbidity and mortality [1]. PH is progressive in COPD, with mean pulmonary arterial pressure increasing over time [2,3]. Understanding variations in susceptibility to PH in patients with COPD could significantly enhance diagnosis, risk stratification and therapy for these patients.Vascular remodelling is the main pathological feature in PH and is mediated via vasoactive molecules [4]. Genes encoding these mediators contain genetic polymorphisms that potentially affect their function and


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