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 alpha-and beta-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 PS Benin haplotype. Our results show no association of MBL2 variants with infectious events, but we observed for the first time that patients carrying the g.In1.1C RANTES variant had a lower risk of recurrence of bacterial infections, suggesting a protective effect conferred by the variant.