Hypertension is a complex disease with strong genetic influences. Essential hypertension has been shown to be associated with insulin resistance. A molecular variant with G-to-A transition at the nucleotide -258 of the liver glucokinase (GCK) promoter was found in diabetic patients. The variant A allele is associated with insulin resistance. We examine the role of this genetic variant in the pathogenesis of hypertension using a population association study. We recruited 205 Taiwanese subjects and they were divided into two groups based on either presence (65 subjects) or absence (140 subjects) of essential hypertension. Genomic DNA was extracted from peripheral leukocytes. Genotypes at this locus were determined by using a polymerase chain reaction restriction fragment length polymorphism. The distribution of genotypic frequency was different between the hypertensive and control groups (P = .009). The frequency of variant A allele was greater in hypertensive subjects than in control (23% v 10%, P = .001). Subjects with at least an A allele had a risk for hypertension by 2.52 times (95% confidence interval 1.29 to 4.91) as compared with those without an A allele. Thus, we first demonstrate the association between the G-to-A variants at the nucleotide -258 of the liver GCK gene and essential hypertension. This may explain the insulin resistance in essential hypertension and the variant A allele as a risk factor for essential hypertension in the Taiwanese population.