Associations between endothelial nitric oxide synthase A/B, angiotensin converting enzyme I/D and serotonin transporter L/S gene polymorphisms with pulmonary hypertension in COPD patients

• Published in: Molecular biology reports Vol. 40; no. 10; pp. 5625 - 5633
• Main Authors: Ulasli, Sevinc Sarinc, Eyuboglu, Fusun Oner, Verdi, Hasibe, Atac, Fatma Belgin
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-10-2013; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Biomedical and Life Sciences; Blood Gas Analysis; C-Reactive Protein - metabolism; Case-Control Studies; Chronic obstructive pulmonary disease; Demography; Electrocardiography; Endothelium; Gene Frequency - genetics; Genetic Association Studies; Genetic Predisposition to Disease; Histology; Humans; Hypertension; Hypertension, Pulmonary - complications; Hypertension, Pulmonary - enzymology; Hypertension, Pulmonary - genetics; Hypertension, Pulmonary - physiopathology; INDEL Mutation - genetics; Life Sciences; Molecular biology; Morphology; Nitric Oxide Synthase Type III - genetics; Peptidyl-Dipeptidase A - genetics; Polymorphism; Polymorphism, Genetic; Pulmonary Disease, Chronic Obstructive - complications; Pulmonary Disease, Chronic Obstructive - enzymology; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - physiopathology; Serotonin Plasma Membrane Transport Proteins - genetics; Severity of Illness Index; Smoking - adverse effects; 5-HTT; eNOS; ACE; Gene polymorphism; Pulmonary hypertension; COPD
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-013-2664-6

Different biochemical pathways and cellular mechanisms play role in the pathogenesis of pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). Alveolar hypoxia is not the only determinant of vascular remodeling, genetic factors are thought to have additive effects. We aimed to investigate the effects of endothelial nitric oxide synthase (eNOS A/B), angiotensin converting enzyme (ACE I/D) and serotonin transporter (5-HTT L/S) gene polymorphisms on development and severity of PH in COPD patients. 50 COPD patients without PH (group 1); 30 COPD patients with PH confirmed with echocardiography (group 2) and 49 healthy subjects (group 3) as control group were included to the study. eNOS A/B, ACE I/D and 5-HTT L/S gene polymorphisms and allele frequencies of COPD patients with and without PH and healthy subjects were determined. Functional parameters and echocardiographic measurements were recorded. Patients with PH were also assessed in two subgroups according to the severity of pulmonary arterial pressure (PAP). Significant differences among three groups in the distribution of 5-HTT genotype and allele frequency were present (respectively
p

=
 0.002
; p

=
 0.021). In group 2, LL and LS genotype rate was 93.3 % with a frequency of 71.2 % L allele and 28.3 % of S allele. 5-HTT LL genotype was present in 88.9 % of patients with PAP ≥50 mmHg significantly (
p
 = 0.012). Other genotype distributions were not significantly different between two subgroups. The results of this study can suggest that COPD patients with L allele of 5-HTT may have higher risk for the development of PH and patients with LL genotype of 5-HTT may present higher PAP. We also demonstrated that eNOS and ACE gene polymorphisms were not associated with the development and severity of PH in our study population. Further studies with larger numbers of patients are needed to explore these relationships.