Endothelin-1 gene and endothelin receptor A gene polymorphisms in severe pulmonary hypertension associated with rheumatic mitral valve disease

Abstract

IntroductionEndothelin-1 (ET-1) gene polymorphisms are implicated in pathogenesis of idiopathic pulmonary arterial hypertensionMaterial and methodsWe studied ET-1 (Lys198Asn and 3A/4A) and endothelin receptor A (ETA) gene (His323His) polymorphisms in 123 subjects with pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD) and 123 healthy controls.ResultsThe mutant homozygous Asn/Asn genotype in Lys198Asn and T/T genotype in His323His polymorphism was more prevalent in PH-MVD group. Presence of Asn/Asn genotype was significantly associated with increased risk (odds ratio 3.9).ConclusionsET-1 and ET<sub>A</sub> gene polymorphisms are prevalent in PH-MVD group suggesting that they may predispose to the development of PH.

Gender differences in genotypic distribution of endothelin-1 gene and endothelin receptor A gene in pulmonary hypertension associated with rheumatic mitral valve disease

“…The mutant homozygous Asn/Asn genotype in Lys198Asn and T/T genotype in His323His polymorphism was more prevalent in Group A (reported previously). 8 When Group A subjects were segregated with respect to gender, the genotype frequency was different in male and female subjects. The mutant and heterozygous genotypes and allele frequencies were more commonly present in females compared to males in Lys198Asn ( p = 0.02) and His323His polymorphisms ( p = 0.01) ( Table 3 ).…”

“…The pulmonary artery end-diastolic pressure (PADP) was calculated from pulmonary regurgitation jet continuous wave Doppler trace. 1 , 8 …”

“…Two polymorphisms, Lys198Asn (rs5370) on ET-1 gene and His323His (rs5333) on ET A gene, were studied and analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR RFLP). 8 The primers and restriction enzymes used for ET-1 and ET A gene polymorphisms were as previously reported. 8 The Lys198Asn PCR product was a 116 base pair (bp) fragment, while the His323His PCR product was a 154 bp fragment.…”

“… 8 The primers and restriction enzymes used for ET-1 and ET A gene polymorphisms were as previously reported. 8 The Lys198Asn PCR product was a 116 base pair (bp) fragment, while the His323His PCR product was a 154 bp fragment. The restriction digestion of the PCR amplicons was done at 37 °C for 15 min and heat inactivation at 65 °C for 5 min with fast digest restriction enzymes Nhe I and BspT I (Thermo Scientific, USA) for study of Lys198Asn and His323His polymorphisms respectively.…”

“… 7 We have previously shown that endothelin-1 (ET-1) gene and endothelin receptor A (ET A ) gene polymorphisms, are significantly more prevalent in patients with PH associated with rheumatic mitral valve disease. 8 …”