Association of adenylyl cyclase 6 rs3730070 polymorphism and hemolytic level in patients with sickle cell anemia

作者：Cita Kizzy Clara; Ferdinand Severine; Connes Philippe; Brudey Laura; Tressieres Benoit; Etienne Julan Maryse; Lemonne Nathalie; Tarer Vanessa; Elion Jacques; Romana Marc^*

来源：Blood Cells, Molecules, and Diseases, 2016, 58: 21-25.

DOI：10.1016/j.bcmd.2016.02.006

• Sickle cell anemia
• Hemolysis
• Adenosine pathway
• Adenylyl cyclase

A recent study suggested that adenosine signaling pathway could promote hemolysis in patients with sickle cell anemia (SCA). This signaling pathway involves several gene coding enzymes for which variants have been described. In this study, we analyzed the genotype-phenotype relationships between functional polymorphisms or polymorphisms associated with altered expression of adenosine pathway genes, namely adenosine deaminase (ada; rs73598374), adenosine A(2b) receptor (adora2b; rs7208480), adenylyl cyclase 6 (adcy6; rs3730071, rs3730070, rs7300155), and hemolytic rate in SCA patients. One hundred and fifty SCA patients were genotyped for adcy6, ada, and adora2b variants as well as alpha-globin gene, a genetic factor known to modulate hemolytic rate. Hematological and biochemical data were obtained at steady-state. Lactate dehydrogenase, aspartate aminotransferase, reticulocytes and total bilirubin were used to calculate a hemolytic index. Genotype-phenotype relationships were investigated using parametric tests and multivariate analysis. SCA patients carrying at least one allele of adcy6 rs3730070-G exhibited lower hemolytic rate than non-carriers in univariate analysis (p = 0.006). The presence of adcy6 rs3730070-G variant was associated with a decreased hemolytic rate in adjusted model for age and alpha-thalassemia (p = 0.032). Our results support a protective effect of adcy6 rs3730070-G variant on hemolysis in SCA patients.

• 出版日期2016-5