title: BMPR2 mutations influence phenotype more obviously in male patients with pulmonary arterial hypertension.
abstract: BACKGROUND
  BMPR2 mutations predispose to idiopathic and heritable pulmonary arterial hypertension (IPAH and HPAH). The influence of BMPR2 mutations on clinical outcome is not concordant in different ethnic groups. Although the BMPR2 mutation 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.
  
  
  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 of BMPR2 mutation carriers and noncarriers were compared. The more severe hemodynamic compromise at diagnosis in BMPR2 mutation carriers versus noncarriers is concordant with other ethnic groups. In the Chinese PAH cohort, BMPR2 mutations 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
  BMPR2 mutations influence phenotype more obviously in male PAH patients. The pathogenesis of female PAH patients is more complicated, and the influence of BMPR2 mutations may be modified by other unknown factors, making disparities in the prognosis between female mutation carriers and noncarriers less evident.
authors.affiliation: Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Wu
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Mao
authors.forename: Ping
authors.initials: P
authors.lastname: Yuan
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Feng-Ling
authors.initials: FL
authors.lastname: Ju
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Jing
mesh_terms: D000328:Adult; D000367:Age Factors; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D005817:Genetic Counseling; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012737:Sex Factors; D016019:Survival Analysis
chemical_list: D052006:Bone Morphogenetic Protein Receptors, Type II