Polymorphisms of the receptor for advanced glycation end products as vasculopathy predictor in sickle cell disease

The genetic variants of the receptor for advanced glycation end products (RAGE) gene have been associated with vascular disease risk. The objective of this work was to explore the association of three single-nucleotide polymorphisms (SNPs) of RAGE gene (374T/A, 429T/C, and G82S) with vascular complications in SCD.

The study was conducted on 40 children with SCD and 40 healthy children served as controls. All participants were genotyped for the three studied RAGE polymorphisms by polymerase chain reaction (PCR).

Regarding 374T/A polymorphism, the frequency of TA, TT genotypes and T allele were higher in patients (p < 0.001). T allele was associated with higher incidence of sickling crisis and stroke (p < 0.05). In the subgroup analyses of 429T/C polymorphism, an association between C allele and SCD vascular complications was observed (p < 0.05). Concerning the frequency of G82S genotypes of RAGE, GG variant was detected in 39 (97.5%) of the patients, as compared with 40 (100%) of controls (p = 0.3). A regression analysis proved that HbS%, serum ferritin, and the -374T and 429C alleles were significant independent predictors of frequent sickling episodes (p < 0.05).

The C allele of -429T/C and T allele of 374T/A RAGE polymorphisms may be considered as predictors for vascular dysfunction in SCD.

The C allele of -429T/C and T allele of 374T/A RAGE polymorphisms may be considered as predictors for vascular dysfunction in SCD patients. To our knowledge, our study is the first exploring the association of three single-nucleotide polymorphisms of RAGE gene (374T/A, 429T/C, and G82S) with vascular complications in SCD. Early identification of patients carrying these genetic variants might be of great importance not only to identify subjects at risk of vasculopathy but also to direct them to RAGE-targeted treatments.