BMPR2Mutations Influence Phenotype More Obviously in Male Patients With Pulmonary Arterial Hypertension

Abstract

Background—BMPR2mutations predispose to idiopathic and heritable pulmonary arterial hypertension (IPAH and HPAH). The influence ofBMPR2mutations on clinical outcome is not concordant in different ethnic groups. Although theBMPR2mutation spectrum and mutation rate in Chinese PAH patients has been reported previously, the influence of genotype on phenotype and whether this influence is associated with sex have not been investigated.Methods and Results—We analyzed data from 305 PAH patients considered as either idiopathic or heritable who underwent genetic counseling in Shanghai Pulmonary Hospital. The clinical, functional, and hemodynamic characteristics ofBMPR2mutation carriers and noncarriers were compared. The more severe hemodynamic compromise at diagnosis inBMPR2mutation carriers versus noncarriers is concordant with other ethnic groups. In the Chinese PAH cohort,BMPR2mutations were associated with a higher risk of mortality after adjustment for age and sex (hazard ratio, 1.971; 95% confidence interval, 1.121–3.466;P=0.018). The overall survival difference between mutation carriers and noncarriers was more obvious in male patients, which was reflected by a higher mortality risk of male mutation carriers than that of male noncarriers after adjustment for age at diagnosis (hazard ratio, 3.702; 95% confidence interval, 1.416–9.679;P=0.008). In females, this trend did not reach statistical significance.Conclusions—BMPR2mutations influence phenotype more obviously in male PAH patients. The pathogenesis of female PAH patients is more complicated, and the influence ofBMPR2mutations may be modified by other unknown factors, making disparities in the prognosis between female mutation carriers and noncarriers less evident.