Gender differences in pulmonary arterial hypertension patients with BMPR2 mutation: a meta-analysis

Abstract

Objective: To investigate the differences in the proportions of BMPR2 mutations in familial hereditary pulmonary arterial hypertension (HPAH) and idiopathic pulmonary arterial hypertension (IPAH) between males and females and the relationship between BMPR2 mutation and PAH severity. Methods: A computer was used to search the electronic Cochrane Library, PubMed/MEDLINE, and EMBASE databases for clinical trials containing information on the relationship between PAH prognosis and BMPR2 mutations through March 2019. After obtaining the data, a meta-analysis was performed using Review Manager Version 5.3 and Stata. Results: A meta-analysis was performed on 17 clinical trials (2198 total patients: 644 male, 1554 female). The results showed that among patients with HPAH and IPAH, the BMPR2 mutation rate is higher in male than in female patients [male group (224/644, 34.78%), female group (457/1554, 29.41%), OR = 1.30, 95% CI: 1.06~1.60, P = 0.01, I 2 = 10%]. Furthermore, haemodynamic and functional parameters were more severe in IPAH and HPAH patients with BMPR2 mutations than in those without, and those with BMPR2 mutation were diagnosed at a younger age. The risk of death or transplantation was higher in PAH patients with BMPR2 mutations than in those without (OR = 2.51, 95% CI: 1.29~3.57, P = 0.003, I 2 = 24%). Furthermore, the difference was significant only in male patients (OR = 5.58, 95% CI: 2.16~14.39, P = 0.0004, I 2 = 0%) and not in female patients (OR = 1.41, 95% CI: 0.75~2.67, P = 0.29, I 2 = 0%). Conclusion: Among patients with HPAH and IPAH, men are more likely to have BMPR2 mutations, which may predict more severe PAH indications and prognosis.

Prevalence and clinical features of bone morphogenetic protein receptor type 2 mutation in Korean idiopathic pulmonary arterial hypertension patients: The PILGRIM explorative cohort

“…This was consistent with the meta-analysis data, suggesting that BMPR2 mutation may play a crucial role in the early development of PAH and severe hemodynamic symptoms [7]. Our study also shows that PAH patients were predominantly women (male:female, 1:2.8), although there was no difference in the proportion of BMPR2 mutation carriers, hemodynamic profiles, or death according to sex [32].…”

Gene Mutation Annotation and Pedigree for Pulmonary Arterial Hypertension Patients in Han Chinese Patients

“…The Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) showed a higher female predominance of PAH irrespective of BMPR2 status, and found that the female-to-male ratio for PAH was 3.9:1 in races other than whites, black and Hispanic [21]. Our study results agreed with previous evidence that suggested female dominance in IPAH or HPAH (Table 1) [17].…”

“…The estimated penetrance in male and female carriers is 14% and 42%, respectively [15,16]. It has been shown that female is the single most important determinant for the penetrance of BMPR2 mutations in PAH [15,16]; male patients were significantly more likely to have BMPR2 mutations than female patients [17]. Similarly, in our study, only one male was found to have the BMPR2 mutation.…”

Novel Advances in Modifying BMPR2 Signaling in PAH

“…BMPR2 carriers with PAH have an earlier disease onset than idiopathic PAH patients [15]. Interestingly, male patients were more likely to possess a BMPR2 mutation than women and develop severe disease in presence of a BMPR2 mutation [16].…”