Objective:To investigate the correlation between polymorphism of Lys198Asn of endothelin(ET)-1 gene exon 5 and ventricular septal defects(VSD) related pulmonary arterial hypertension(PAH),and risk factors of PAH. Methods:Genotypes were determined by the PCR-restriction fragment length polymorphism(PCR-RFLP) method in 140 VSD related PAH cases and 140 non-PAH controls. Results:①The frequencies of GT and TT genotypes in PAH group were significantly higher than non-PAH group (43.6% vs 33.6%, adjusted OR=1.78,P < 0.05;10.7% vs 3.6%,adjusted OR=3.34,P < 0.01; respectively);②The frequency of GT+TT genotypes in PAH group was significantly higher than that of the controls(54.3% vs 37.2%, adjusted OR=1.94,P < 0.01);③The T allele frequency in PAH group was significantly higher than that in the controls(32.5% vs 20.4%, P < 0.01). Conclusion: ET-1 gene Lys198Asn polymorphism is associated with and may be a new risk factor of PAH.