Journal Article Research Support, Non-U.S. Gov't Epublish
PubMed: 39738165 DOI: 10.1038/s41598-024-76480-0
The endocannabinoid system's genetic polymorphisms in sickle cell anemia patients.
Sci Rep 14(1):31562
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
Affiliations
- Institute of Biosciences, Humanities and Exact Sciences, Biosciences Postgraduate Program, UNESP - São Paulo State University, São José do Rio Preto, Brazil.
- Molecular Biology and Genetics Laboratory (LGBM), UFMS - Federal University of Mato Grosso do Sul, Três Lagoas, Brazil.
- Molecular Biology and Genetics Laboratory (LGBM), UFMS - Federal University of Mato Grosso do Sul, Três Lagoas, Brazil.
- Genetics Postgraduate Program, UFPE - Federal University of Pernambuco, Recife, Brazil.
- HEMOPE - Hematology and Hemotherapy Foundation, Recife, Brazil.
- Institute of Biosciences, Humanities and Exact Sciences, Biosciences Postgraduate Program, UNESP - São Paulo State University, São José do Rio Preto, Brazil.
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 -α-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.
MeSH
Cells, Anemia, Sickle Cell, Anemia, Priapism, Thalassemia, Receptor, Cannabinoid, Cb2, Polymorphism, Genetic, Genotype, Endocannabinoids, Cannabinoids, Mutation