Berti Amanda Cristina Meneguetti, de Castro Vanessa da Silveira Ramos, Arcanjo Gabriela Silva, da Silva Araujo Aderson, Lucena-Araujo Antonio Roberto, Bezerra Marcos André Cavalcanti, Gazarini Lucas, da Silva Danilo Grünig Humberto, Belini-Júnior Edis
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.
Sci Rep. 2024 Dec 30;14(1):31562. doi: 10.1038/s41598-024-76480-0.
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.
镰状细胞贫血（SCA）是一种单基因血液疾病，其病理生理学复杂且具有多因素性。内源性大麻素系统（ECS）可能是调节SCA并发症（如阴茎异常勃起）的一个候选因素，因为它已在造血、血小板聚集和免疫反应中显示出重要作用。我们评估了巴西SCA队列中与ECS相关的单核苷酸多态性（SNP）（脂肪酸酰胺水解酶基因FAAH的rs324420、单酰甘油脂肪酶基因MAGL的rs604300、大麻素受体1基因CNR1的rs7766029和大麻素受体2基因CNR2的rs35761398）与阴茎异常勃起的关联。该研究纳入了138名SCA患者（n = 80名有阴茎异常勃起，n = 58名无阴茎异常勃起）。通过高效液相色谱法检测SCA，并用聚合酶链反应-限制性内切酶分析（PCR-RE）确认血红蛋白SS基因型。用多重聚合酶链反应检测α地中海贫血突变，并用TaqMan基因分型检测法进行SNP基因分型。我们观察到，有阴茎异常勃起的患者中-α地中海贫血突变的频率低于无此并发症的患者（p < 0.001），在调整后的多变量分析中，CNR2 rs35761398的TT-CC基因型与发生阴茎异常勃起的几率较低相关（比值比OR = 0.386 [0.175 - 0.854]，p = 0.019），且随着时间推移其风险较低（风险比HR = 0.634 [0.402 - 0.987]，p = 0.049）。SCA缺血性阴茎异常勃起与血管舒张/血管收缩途径失衡有关，如RhoA/ Rho激酶（ROCK）信号传导降低。由于激活2型大麻素受体（CB2）会降低RhoA的激活，我们提出一种涉及CB2的SCA阴茎异常勃起新方法。
