With the G5665T (rs5370) polymorphism on the ET-1 gene however, we found a statistically significant difference in both the genotypic (p Z 2.84E-12) and allelic (p Z 2.20E-12) frequencies of the mutant variant between sickle cell and control groups (Fig. 1). Comparing variants, we found the highest genotypic (40.5% versus 66.5%) and allelic (52.4% versus 80.9%) frequencies on the homozygous mutant loci (ET-1 5665T>T) for both sickle cell disease and control groups, contrary to previous observation among Africans with sickle cell disease.20 That the highest frequency for the G5665T (rs5370) homozygous mutant variant was found among controls and not sickle cell disease patients, calls into question previous reports of endothelin-1 poly- morphisms, as being implicated in sickle cell disease path- ophysiology and clinical variability. This higher frequency of endothelin-1 homozygous mutant variants in African Amer- ican controls reveal a potential unrelated role, probably hitherto unknown, of this variant in possibly other disease conditions but not sickle cell disease.25,31 This difference, compared to our African population potentially also reflects the role of ancestry, traceable either to the Afroasiatic and Nilo-Saharan speaking populations of coastal West Africa or the Niger-Kordofanian groups of inland West Africa.