title: Haplotype analysis of the human renin gene and essential hypertension.
abstract: The human renin gene is an attractive candidate for involvement in the underlying cause of essential hypertension (EH). Despite extensive examination, the relation between the renin gene and hypertension remains unclear. The aims of the present study were to discover new genetic markers of EH and to investigate the relations between polymorphisms of the renin gene and EH in the Japanese. Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we isolated 3 novel variants of the renin gene; a single nucleotide polymorphism (SNP) in intron 4 (T+17int4G), a variable number of tandem repeats (VNTR) polymorphism in intron 7, and a missense mutation in exon 9 (G1051A). We performed an association study with these polymorphisms in 212 patients with EH and 209 age-matched normotensive (NT) subjects. The frequency of genotypes VNTR and T+17int4G did not differ significantly between the 2 groups, whereas the overall distribution of G1051A was significantly different between EH and NT. Haplotype analysis revealed that the overall distribution of haplotypes differed significantly between the EH and NT groups. PRA levels in patients with EH with the G/G genotype were significantly higher than in subjects with EH with G/A and A/A genotypes. These data suggest that the missense mutation in exon 9 may affect the enzymatic function of renin and consequently may be involved in the etiology of hypertension.
authors.affiliation: Division of Receptor Biology, Advanced Medical Research Center, the Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Buaijiaer
authors.initials: B
authors.lastname: Hasimu
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakayama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mizutani
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Izumi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Asai
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kokubun
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ozawa
mesh_terms: D000328:Adult; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D012083:Renin / Q000097:blood / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D004247:DNA; D012083:Renin