We isolated the 5'-flanking region of the type A human natriuretic peptide receptor gene (hNPRA) using thermal asymmetric interlaced polymerase chain reaction (TAIL-PCR). The 2.1-kb 5' sequence upstream of the hNPRA gene lacks a TATA box but contains three potential Sp1-binding sites and an inverted CCAAT box. Moreover, we discovered a novel dinucleotide repeat marker approximately 300 bp upstream of the start codon. Using this microsatellite marker, we performed an association study in patients with essential hypertension (EH). One hundred twenty-five patients with essential hypertension and 125 age-matched subjects with normal blood pressure were studied. The number of TC/GA repeats of the three alleles ranged from 10 to 12 repeats in the 250 unrelated Japanese subjects. The allele frequency distribution in the two groups were not significantly different. Thus, the microsatellite polymorphism in the hNPRA gene is not associated with EH.