Effects of RANTES and MBL2 gene polymorphisms in sickle cell disease clinical outcomes: association of the g.In1.1T>C RANTES variant with protection against infections.

Sickle cell anemia (SCA) is a single-gene mutation genetic disease characterized by a highly variable clinical presentation. Genetic modifiers of the general outcome have been reported, some of them linked to the α-and β-globin gene clusters. In addition, polymorphisms linked to various genes have been associated with specific complications of the disease. We studied the polymorphisms of two candidate genes, MBL2 (Mannose-Binding Lectin 2) and chemokine RANTES (Regulated upon Activation, normal T cell-Expressed and Secreted), in relation to infectious complications in a series of 115 patients with SCA living in two different environments: Benin and France. All the patients were identified at birth and followed for 5 years. All were homozygotes for the βS Benin hapio- type. Our results show no association of MBL2 variants with infectious events, but we observed for the first time that patients carrying the g.ln1.1C RANTES variant had a lower risk of recurrence of bacterial infections, suggesting a protective effect conferred by the variant.