Endothelin-1 but not endothelial nitric oxide synthase polymorphisms are implicated in sickle cell disease (P3311)

Abstract

Abstract Sickle cell disease (SCD) shows marked variability in severity among individuals; this variability probably linked to differential expression of adhesion molecules. Polymorphisms of the endothelial nitric oxide synthase (eNOS) have been implicated in disease severity, potentially delineating vascular complications. There is paucity of information on endothelin-1 (ET-1) diversity and disease severity or ethnic stratification. We examined genomic diversity and estimated haplotype frequency of eNOS and ET-1 polymorphisms in children with SCD. Thirteen SCD children (HbSS) and 176 adult and pediatric controls (HbAA) from Mali were recruited. Genotypic analysis of eNOS variants (T786C, Glu298Asp and intron 4) and ET-1 (G5665T) was carried out with a PCR-RFLP assay. Our results show the frequency distribution and allelic diversity of eNOS and ET-1 variants. Endothelin-1 (G5665T) mutant form was the most frequent, and probably most significant among children with SCD, though the distribution is out of Hardy-Weinberg equilibrium (P=0.0008). eNOS variants showed no difference between SCD and controls. We show that eNOS variants are less frequent, and may have no functional significance in SCD. Additionally, eNOS allele and genotype frequencies are not significantly different in cases and controls. Association between ET-1 and eNOS variants in African versus African American SCD children will be explored and the reason(s) for the HWE deviation will be investigated.