title: Association of adenylyl cyclase 6 rs3730070 polymorphism and hemolytic level in patients with sickle cell anemia.
abstract: 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 A2b receptor (adora2b; rs7208480), adenylyl cyclase6 (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.
authors.affiliation: Inserm UMR 1134, Hôpital Ricou, CHU de Pointe-à-Pitre, F-97157 Guadeloupe, France; Laboratoire d'Excellence du Globule Rouge (LABEX GR-Ex), PRES Sorbonne Paris Cité, F-a, Paris, France.
authors.forename: Kizzy-Clara
authors.initials: KC
authors.lastname: Cita
authors.affiliation: Inserm UMR 1134, Hôpital Ricou, CHU de Pointe-à-Pitre, F-97157 Guadeloupe, France; Laboratoire d'Excellence du Globule Rouge (LABEX GR-Ex), PRES Sorbonne Paris Cité, F-a, Paris, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Ferdinand
authors.affiliation: Inserm UMR 1134, Hôpital Ricou, CHU de Pointe-à-Pitre, F-97157 Guadeloupe, France; Laboratoire d'Excellence du Globule Rouge (LABEX GR-Ex), PRES Sorbonne Paris Cité, F-a, Paris, France; Institut Universitaire de France, F-75006 Paris, France; Laboratoire CRIS EA647, Equipe "Biologie Vasculaire et du Globule Rouge", Université Lyon 1, F-69100 Villeurbanne, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Connes
authors.affiliation: Inserm UMR 1134, Hôpital Ricou, CHU de Pointe-à-Pitre, F-97157 Guadeloupe, France; Laboratoire d'Excellence du Globule Rouge (LABEX GR-Ex), PRES Sorbonne Paris Cité, F-a, Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Brudey
authors.affiliation: Centre d'Investigation Clinique Antilles Guyane CIC 14-24 Inserm, CHU de Pointe-à-Pitre, Guadeloupe, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Tressières
authors.affiliation: Unité Transversale de la Drépanocytose, Centre de référence maladies rares pour la drépanocytose aux Antilles-Guyane, CHU de Pointe-à-Pitre, F-97157 Pointe-à-Pitre, Guadeloupe, France.
authors.forename: Maryse
authors.initials: M
authors.lastname: Etienne-Julan
authors.affiliation: Unité Transversale de la Drépanocytose, Centre de référence maladies rares pour la drépanocytose aux Antilles-Guyane, CHU de Pointe-à-Pitre, F-97157 Pointe-à-Pitre, Guadeloupe, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lemonne
authors.affiliation: Unité Transversale de la Drépanocytose, Centre de référence maladies rares pour la drépanocytose aux Antilles-Guyane, CHU de Pointe-à-Pitre, F-97157 Pointe-à-Pitre, Guadeloupe, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Tarer
authors.affiliation: Laboratoire d'Excellence du Globule Rouge (LABEX GR-Ex), PRES Sorbonne Paris Cité, F-a, Paris, France; Inserm UMR 1134, F-75739 Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Elion
authors.affiliation: Inserm UMR 1134, Hôpital Ricou, CHU de Pointe-à-Pitre, F-97157 Guadeloupe, France; Laboratoire d'Excellence du Globule Rouge (LABEX GR-Ex), PRES Sorbonne Paris Cité, F-a, Paris, France. Electronic address: marc.romana@inserm.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Romana
mesh_terms: D000241:Adenosine / Q000235:genetics; D000262:Adenylyl Cyclases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000235:genetics* / Q000473:pathology*; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D006461:Hemolysis; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult; D017085:alpha-Thalassemia / Q000235:genetics / Q000473:pathology
chemical_list: D000262:Adenylyl Cyclases; C121100:adenylyl cyclase 6; D000241:Adenosine
keywords: Adenosine pathway; Adenylyl cyclase; Hemolysis; Sickle cell anemia