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Clinical and Genetic Predictors of Priapism in Sickle Cell Disease: Results From the Recipient Epidemiology and Donor Evaluation Study III Brazil Cohort Study

key information

source: The Journal of Sexual Medicine

year: 2019

authors: Mina Cintho Ozahata, Grier P Page, Yuelong Guo, João Eduardo Ferreira, Carla Luana Dinardo, Anna Bárbara F Carneiro-Proietti, Paula Loureiro, Rosimere Afonso Mota, Daniela O W Rodrigues, André Rolim Belisario, Claudia Maximo, Miriam V Flor-Park, Brian Custer, Shannon Kelly, Ester Cerdeira Sabino

summary/abstract:

Introduction:
Priapism is the persistent and painful erection of the penis and is a common sickle cell disease (SCD) complication.

Aim:
The goal of this study was to characterize clinical and genetic factors associated with priapism within a large multi-center SCD cohort in Brazil.

Methods:
Cases with priapism were compared to SCD type-matched controls within defined age strata to identify clinical outcomes associated with priapism. Whole blood single nucleotide polymorphism genotyping was performed using a customized array, and a genome-wide association study (GWAS) was conducted to identify single nucleotide polymorphisms associated with priapism.

Main Outcome Measure:
Of the 1,314 male patients in the cohort, 188 experienced priapism (14.3%).

Results:
Priapism was more common among older patients (P = .006) and more severe SCD genotypes such as homozygous SS (P < .0001). In the genotype- and age-matched analyses, associations with priapism were found for pulmonary hypertension (P = .05) and avascular necrosis (P = .01). The GWAS suggested replication of a previously reported candidate gene association of priapism for the gene transforming growth factor beta receptor 3 (TGFBR3) (P = 2 × 10-4).

Clinical Implications:
Older patients with more severe genotypes are at higher risk of priapism, and there is a lack of consensus on standard treatment strategies for priapism in SCD.

Strengths & limitations:
This study characterizes SCD patients with any history of priapism from a large multi-center cohort. Replication of the GWAS in an independent cohort is required to validate the results.

Conclusion:
These findings extend the understanding of risk factors associated with priapism in SCD and identify genetic markers to be investigated in future studies to further elucidate priapism pathophysiology.

organization: University of São Paulo, Brazil; RTI International, USA; Pró-Sangue Foundation, Brazil; Hemominas Foundation, Brazil; Hemope Foundation and University of Pernambuco, Brazil; Hemorio Foundation, Brazil; Vitalant Research Institute, USA; UCSF Benioff Children's Hospital, USA

DOI: 10.1016/j.jsxm.2019.09.012

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