
<ArticleTitle>Systematic screening of <prot>type B human natriuretic peptide receptor</prot> gene polymorphisms and association with essential hypertension.</ArticleTitle>
<AbstractText><prot>C-type natriuretic peptide</prot> (<prot>CNP</prot>) dilates arteries, lowers blood pressure and inhibits proliferation of vascular smooth muscle cells via the <prot>type B natriuretic peptide receptor</prot> (<prot>NPRB</prot>). The <prot>CNP</prot>-<prot>NPRB</prot> system may play a crucial role in the development of cardiovascular disease. We recently determined the structure of the human <prot>NPRB</prot> gene. In the present study, our objectives are to identify the polymorphisms of the <prot>NPRB</prot> gene and investigate the association of this gene with essential hypertension (EH). We used the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique to study the <prot>NPRB</prot> gene polymorphism, and conducted an association study using a novel polymorphic marker. PCR-SSCP analysis of all 22 exons was done in 90 subjects, and abnormally-migrating bands were observed in the analyses of exon 11 and intron 18. Direct sequencing of these DNA fragments revealed the following sequence alterations: a C to T transition at nucleotide (nt) 2077 in exon 11 and a 9-bp insertion/deletion (I/D) in intron 18. PCR-restriction fragment length polymorphism analysis (PCR-RFLP) was developed to detect the C2077T transition. PCR-RFLP analyses of healthy subjects revealed that the C2077T polymorphism had complete linkage to GT repeats in intron 2 reported previously. The I/D polymorphism was identified by polyacrylamide gel electrophoresis, and it was not linked to any known polymorphic alleles of this gene. Therefore, the possible association between the I/D polymorphism and EH was investigated. A total of 123 individuals with EH and 123 age-matched normotensive control subjects were studied. Overall distributions of allele frequencies in the two groups were not significantly different. Although the I/D polymorphism in intron 18 of the <prot>NPRB</prot> gene was not associated with EH, the results of this study, which identified two novel polymorphisms in the human <prot>NPRB</prot> gene, will facilitate further genetic analysis of this gene and cardiovascular disease.</AbstractText>
