Genetic analysis of the atrial natriuretic peptide gene in essential hypertension

Atrial natriuretic peptide (ANP) plays an important role in the regulation of blood pressure through sodium-water homoeostasis. Accordingly, several i nvestigators have raised the question of whether the gene encoding ANP is i nvolved in the aetiology of essential hypertension or related phenotypes su ch as salt sensitivity. Most of the studies have used anonymous polymorphic markers of the gene, and made inconclusive claims about the disease releva nce of ANP. Therefore, in order to find sequence variations with potential functional significance and to characterize the pattern of linkage disequil ibrium between polymorphisms, we screened a 3368-bp genomic fragment of ANP . Subsequently we tested the association of detected polymorphisms with pla sma ANP levels and with hypertension status. Two new polymorphisms were ide ntified, in the 5'-untranslated region and exon I respectively, as well as th ree previously reported polymorphisms in intron 2 and exon 3. When analy sed in 102 healthy normotensive subjects, none of the polymorphisms appeare d to significantly affect plasma ANP levels. A case-control study in a Japa nese population (255 hypertensive and 225 normotensive individuals) reveale d a marginally significant association (P = 0.026) between an ANP polymorph ism located in the 5'-untranslated region (C-664G) and hypertension, but no association for the other polymorphisms. Each of the uncommon variants has an allele frequency of less than 10% in Japanese people, which may have ha mpered our detection of a significant association between AN P variants and hypertension status (and plasma ANP levels). The pathophysiological releva nce of ANP, however, needs to be further defined in relation to hypertensio n-associated phenotypes, and also should be examined in different ethnic gr oups.