Improved Survival of Patients with Pulmonary Arterial Hypertension with <i>BMPR2</i> Mutations in the Last Decade

Isobe, Satoshi; Kataoka, Masaharu; Aimi, Yuki; Gamou, Shinobu; Satoh, Tsuyoshi; Fukuda, Keiichi

doi:10.1164/rccm.201601-0158le

Cited by 13 publications

(14 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In terms of the prognosis for the BMPR2 mutation carriers, a meta-analysis study demonstrated that all-cause mortality and lung transplant-free survival were worse in the BMPR2 mutation carriers compared with the non-carriers, especially among younger patients at diagnosis, 2 while our previous report demonstrated that in patients who needed PGI 2 infusion owing to severe clinical conditions, BMPR2 mutation carriers showed a better prognosis than non-carriers. 18 These findings may raise the possibility that the RNF213 p.Arg4810Lys variant, which is identified mainly in the East Asian population, may play an important role in the poorer outcomes of the BMPR2 mutation non-carriers, demonstrated in our previous study. 18 Importantly, our findings demonstrated that BMPR2-associated and RNF213 p.Arg4810Lys variant-associated PAH have almost similar phenotypes, as observed in our pathological findings, but the underlying mechanisms should be quite different, i.e., the genetic heterogeneity in PAH.…”

Section: Discussionmentioning

confidence: 58%

“…18 These findings may raise the possibility that the RNF213 p.Arg4810Lys variant, which is identified mainly in the East Asian population, may play an important role in the poorer outcomes of the BMPR2 mutation non-carriers, demonstrated in our previous study. 18 Importantly, our findings demonstrated that BMPR2-associated and RNF213 p.Arg4810Lys variant-associated PAH have almost similar phenotypes, as observed in our pathological findings, but the underlying mechanisms should be quite different, i.e., the genetic heterogeneity in PAH. Furthermore, our Kaplan-Meier analysis demonstrated that the event-free rate since the diagnosis of PAH was significantly poorer in the RNF213 p.Arg4810Lys variant carriers compared with the carriers with other rare RNF213 variants, suggesting the p.Arg4810Lys variant is different from any other rare RNF213 variant and should lead to specific mechanisms in the underlying RNF213-signaling pathway.…”

Section: Discussionmentioning

confidence: 58%

See 1 more Smart Citation

Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension

Hiraide

Kataoka

Suzuki

et al. 2020

The Journal of Heart and Lung Transplantation

Self Cite

View full text Add to dashboard Cite

BACKGROUND: A variant of c.14429G>A (p.Arg4810Lys, rs112735431) in the ring finger protein 213 gene (RNF213; NM_001256071.2) has been recently identified as a risk allele for pulmonary arterial hypertension (PAH). PAH can be added as a new member of RNF213-associated vascular diseases, which include Moyamoya disease and peripheral pulmonary stenosis. Our aim was to identify the clinical features and outcomes of PAH patients with this variant. METHODS: Whole-exome sequencing was performed in 139 idiopathic (or possibly heritable) PAH patients. RESULTS: The RNF213 p.Arg4810Lys variant was identified in a heterozygous state in 11 patients (7.9%). Time-course changes in hemodynamics after combination therapy in the patients with the RNF213 p.Arg4810Lys variant were significantly poorer compared with those carrying the bone morphogenic protein receptor type 2 (BMPR2) mutation (n = 36) (comparison of changes in mean pulmonary arterial pressure, p = 0.007). The event-free rate of death or lung transplantation was significantly poorer in RNF213 p.Arg4810Lys variant carriers than in BMPR2 mutation carriers (5-year event-free rate since the introduction of prostaglandin I 2 infusion, 0% vs 93%, respectively; p < 0.001).

show abstract

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 58%

Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension

Hiraide

Kataoka

Suzuki

et al. 2020

The Journal of Heart and Lung Transplantation

Self Cite

View full text Add to dashboard Cite

show abstract

“…Then, the full text of each of the remaining 42 articles was retrieved for further review to determine whether they met the predetermined criteria. Finally, 17 papers were identified and included in the present study [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24].…”

Section: Resultsmentioning

confidence: 99%

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

Zhu

Zhang

et al. 2020

Respir Res

View full text Add to dashboard Cite

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.

show abstract

“…All other cohorts enrolled familial cases to a similar degree (6 to 22%). The overall prevalence of BMPR2 mutations in Korean IPAH patients was 22%, which is slightly higher than observed in Chinese and lower than in Japanese cohorts (Fig 2) [19,22,24,28]. Data from Asian populations are limited, and the prevalence of BMPR2 mutation differs between Japanese (36-41%) and Chinese (16-29%) studies (Fig 2) [19,25,27,29].…”

Section: Discussionmentioning

confidence: 85%

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

et al. 2020

View full text Add to dashboard Cite

Background Pulmonary arterial hypertension (PAH) is a progressive chronic disease with poor outcomes. One reason for poor prognosis is the lack of understanding regarding individual variability in response to treatment. Idiopathic PAH (IPAH) patients with bone morphogenetic protein receptor type 2 (BMPR2) mutations have distinct phenotypes that are crucial for individualized therapy but evidence regarding their prevalence and clinical features in the Korean population is lacking. Therefore, the present study aimed to screen Korean IPAH patients for BMPR2 mutations and analyze their clinical phenotypes. Methods We enrolled 73 unrelated IPAH patients for BMPR2 mutation screening between March 2010 to November 2015 from 11 hospitals in Korea. Thirty-three lineal family members from 6 families of BMPR2 mutation carriers were also screened.

show abstract

Improved Survival of Patients with Pulmonary Arterial Hypertension with BMPR2 Mutations in the Last Decade

Cited by 13 publications

References 9 publications

Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension

Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension

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

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

Contact Info

Product

Resources

About