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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Nature Portfolio
2024-12-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-76480-0 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Amanda Cristina Meneguetti Berti |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-f9947c8a59344e4eabc55b54d0a65de5 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-f9947c8a59344e4eabc55b54d0a65de52025-01-05T12:24:14ZengNature PortfolioScientific Reports2045-23222024-12-011411910.1038/s41598-024-76480-0The endocannabinoid system’s genetic polymorphisms in sickle cell anemia patientsAmanda Cristina Meneguetti Berti0Vanessa da Silveira Ramos de Castro1Gabriela Silva Arcanjo2Aderson da Silva Araujo3Antonio Roberto Lucena-Araujo4Marcos André Cavalcanti Bezerra5Lucas Gazarini6Danilo Grünig Humberto da Silva7Edis Belini-Júnior8Institute of Biosciences, Humanities and Exact Sciences, Biosciences Postgraduate Program, UNESP - São Paulo State UniversityMolecular Biology and Genetics Laboratory (LGBM), UFMS - Federal University of Mato Grosso do SulGenetics Postgraduate Program, UFPE - Federal University of PernambucoHEMOPE - Hematology and Hemotherapy FoundationGenetics Postgraduate Program, UFPE - Federal University of PernambucoGenetics Postgraduate Program, UFPE - Federal University of PernambucoMolecular Biology and Genetics Laboratory (LGBM), UFMS - Federal University of Mato Grosso do SulInstitute of Biosciences, Humanities and Exact Sciences, Biosciences Postgraduate Program, UNESP - São Paulo State UniversityMolecular Biology and Genetics Laboratory (LGBM), UFMS - Federal University of Mato Grosso do SulAbstract 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.https://doi.org/10.1038/s41598-024-76480-0PriapismHemolysisPrognosticEndocannabinoids |
| spellingShingle | 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 The endocannabinoid system’s genetic polymorphisms in sickle cell anemia patients Scientific Reports Priapism Hemolysis Prognostic Endocannabinoids |
| title | The endocannabinoid system’s genetic polymorphisms in sickle cell anemia patients |
| title_full | The endocannabinoid system’s genetic polymorphisms in sickle cell anemia patients |
| title_fullStr | The endocannabinoid system’s genetic polymorphisms in sickle cell anemia patients |
| title_full_unstemmed | The endocannabinoid system’s genetic polymorphisms in sickle cell anemia patients |
| title_short | The endocannabinoid system’s genetic polymorphisms in sickle cell anemia patients |
| title_sort | endocannabinoid system s genetic polymorphisms in sickle cell anemia patients |
| topic | Priapism Hemolysis Prognostic Endocannabinoids |
| url | https://doi.org/10.1038/s41598-024-76480-0 |
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