Abstract
Genetic polymorphisms are variations in DNA sequences which can influence either disease susceptibility, severity, or prognosis. Pulmonary arterial hypertension (PAH) is one of the complications that occurs in certain patients who have atrial septal defect (ASD). This study seeks to determine the association of gene polymorphisms with the pathogenesis of PAH in ASD patients. This study was conducted on 30 ASD patients with PAH, and 50 ASD patients who were not diagnosed with PAH. All respondents were Malay. Patients were selected based on stringent inclusion and exclusion criteria. Molecular analyses were done to detect the genetic polymorphisms of angiotensin converting enzyme (ACE I/D), serotonin transporter (5-HTTLPR), endothelial nitric oxide synthase (eNOS) G894T, and eNOS 4b/4a. The genotypes of these genetic polymorphisms were determined using conventional PCR and PCR-RFLP methods. The PCR products were analysed using agarose gel electrophoresis. Statistical analysis was done using SPSS Version 22. Clinical characteristics, such as the diameter of ASD, mean arterial pressure (MAP), and mean pulmonary artery pressure (mPAP) differed significantly (p < 0.05). Based on the statistical analysis, ACE I/D, eNOS G894T, and eNOS 4b/4a do not contribute to the progression of PAH amongst ASD patients (p > 0.05). However, the L allele of the 5-HTTLPR gene polymorphism may have an affect on the development of PAH in ASD patients (p < 0.05).
Highlights
Atrial septal defect (ASD) is a congenital heart defect caused by the presence of an interatrial communication
Candidate gene analysis enables the identification of the presence of known gene variations of candidate genes (ACE, endothelial nitric oxide synthase (eNOS) and 5-HTTLPR) that may be implicated in the pathogenesis of pulmonary arterial hypertension (PAH)
We found that the L allele of the 5-HTTLPR gene polymorphism was associated with an increased risk of possible PAH
Summary
Atrial septal defect (ASD) is a congenital heart defect caused by the presence of an interatrial communication. ASD is usually asymptomatic in children, but in adults, it may be complicated by pulmonary arterial hypertension (PAH). ASD causes left-to-right shunts [4]. The direction and magnitude of the shunting strongly depends on the size of the defect and the relative compliance of the left and right that can change over time [2]. The incidence of PAH is around 2 cases per a million population per year, and can affect individuals at any age, but is most common among adults between 36 to 50 years of age [1]. Patients with ASD are usually asymptomatic and tend to develop PAH after turning 30. In some patients, the onset of PAH is noted earlier, and even in small ASD with insignificant left to right shunts. It is believed that in this group of patients, the pathophysiology of PAH is more similar to those with idiopathic PAH
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