Using different methodological approaches (single-locus, haplotypic, and multilocus effects) and study designs (family-based and unrelated case-control designs), our investigation did not suggest an important contribution of the studied markers in the risk of essential hypertension in quilombos. However, our data highlight the potential of two multilocus effects: (i) the effect of both GNB3 variants (C825T and G-350A polymorphisms) on DBP levels in a family-based design and (ii) the significant NOS3-GRK4 interaction also in relation to DBP levels in the unrelated case-control design. This evidence concerns the gene NOS3 and essential hypertension.