title: A novel variable number of tandem repeat of the natriuretic peptide precursor B gene's 5'-flanking region is associated with essential hypertension among Japanese females.
abstract: BACKGROUND
  Brain natriuretic peptide (BNP) acts primarily as a cardiac hormone; it is produced by the ventricle and has both vasodilatory and natriuretic actions. Therefore, the BNP gene is thought to be a candidate gene for essential hypertension (EH). The present study identified variants in the 5'-flanking region of natriuretic peptide precursor B (NPPB) gene and assessed the relationship between gene variants and EH.
  
  
  METHODS
  The polymerase chain reaction-single strand conformation polymorphism method and nucleotide sequencing were used to identify variants.
  
  
  RESULTS
  A novel variable number of tandem repeat (VNTR) polymorphism in the 5'-flanking region (-1241 nucleotides from the major transcriptional initiation site) was discovered. This VNTR polymorphism is a tandem repeat of the 4-nucleotide sequence TTTC. There were 8 alleles, ranging from 9-repeat to 19-repeat. An association study was done involving 317 EH patients and 262 age-matched normotensive (NT) subjects. The 11-repeat allele was the most frequent (88.2%); the 16-repeat allele was the second most frequent (10.5%) in the NT group. The observed and expected genotypes were in agreement with the predicted Hardy-Weinberg equilibrium values (P=0.972). Among females, the overall distribution of genotypes was significantly different between the EH and NT groups (p=0.039). The frequency of the 16-repeat allele was significantly lower in the female EH group (6.5%) than in the female NT group (12.2%, p=0.046).
  
  
  CONCLUSIONS
  The 16-repeat allele of the VNTR in the 5'-flanking region of NPPB appears to be a useful genetic marker of EH in females.
authors.affiliation: Division of Nephrology and Endocrinology, Department of Medicine, Nihon University School of Medicine, Ooyaguchi-kamimachi, Itabashi-ku, Tokyo, Japan.
authors.forename: Kotoko
authors.initials: K
authors.lastname: Kosuge
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakayama
authors.forename: Noriko
authors.initials: N
authors.lastname: Aoi
authors.forename: Mikano
authors.initials: M
authors.lastname: Sato
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Izumi
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D024506:5' Flanking Region / Q000235:genetics*; D000328:Adult; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D015992:Body Mass Index; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007564:Japan; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008875:Middle Aged; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D020097:Natriuretic Peptide, Brain / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA
chemical_list: D020097:Natriuretic Peptide, Brain