The endocannabinoid system’s genetic polymorphisms in sickle cell anemia patients

The endocannabinoid system’s genetic polymorphisms in sickle cell anemia patients

Abstract Sickle cell anemia (SCA) is a monogenic blood disease with complex and multifactorial pathophysiology. The endocannabinoid system (ECS) could be a candidate for modulating SCA complications, such as priapism, as it has demonstrated an essential role in hematopoiesis, platelet aggregation, a...

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Main Authors: Amanda Cristina Meneguetti Berti, Vanessa da Silveira Ramos de Castro, Gabriela Silva Arcanjo, Aderson da Silva Araujo, Antonio Roberto Lucena-Araujo, Marcos André Cavalcanti Bezerra, Lucas Gazarini, Danilo Grünig Humberto da Silva, Edis Belini-Júnior
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Scientific Reports
Subjects:
Priapism
Hemolysis
Prognostic
Endocannabinoids
Online Access:https://doi.org/10.1038/s41598-024-76480-0
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Summary:Abstract Sickle cell anemia (SCA) is a monogenic blood disease with complex and multifactorial pathophysiology. The endocannabinoid system (ECS) could be a candidate for modulating SCA complications, such as priapism, as it has demonstrated an essential role in hematopoiesis, platelet aggregation, and immune responses. We evaluated the association of ECS-related single nucleotide polymorphisms (SNP) (FAAH rs324420, MAGL rs604300, CNR1 rs7766029, and CNR2 rs35761398) with priapism in a Brazilian SCA cohort. The study involved 138 SCA patients (n = 80 with priapism and n = 58 without priapism). SCA was detected with HPLC, and the Hb SS genotype was confirmed with PCR-RE. Alpha thalassemia mutations were detected with Multiplex-PCR, and SNP genotyping was performed using TaqMan genotyping assays. We observed a lower frequency of -α3.7kb-thalassemia mutation in patients with priapism than in patients without this complication (p < 0.001), and in adjusted multivariate analyses TT-CC genotype of CNR2 rs35761398 was associated with a lower chance of developing priapism (OR = 0.386 [0.175–0.854], p = 0.019) and a lower risk of it over time (HR = 0.634 [0.402–0.987], p = 0.049). The SCA ischemic priapism is related to unbalanced vasodilation/vasoconstriction pathways, such as decreased RhoA/Rho-kinase (ROCK) signaling. Since activating the type 2 cannabinoid receptor (CB2) decreases RhoA activation, we suggest a novel approach to SCA priapism involving CB2.
ISSN:2045-2322

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