title: Association of TNFRSF4 gene polymorphisms with essential hypertension.
abstract: BACKGROUND
  Essential hypertension is a complex disorder that results from the interaction of a number of susceptibility genes and environmental factors. The TNFRSF4 (tumor necrosis factor receptor superfamily, member 4) gene was one of the genes that showed altered renal expression in long-term salt loading in mice. Moreover, association of the TNFRSF4 and TNFSF4 (tumor necrosis factor (ligand) superfamily, member 4) genes with myocardial infarction was recently reported. Since essential hypertension is a well-known risk factor for myocardial infarction, we hypothesized that TNFRSF4 could be a susceptibility gene for essential hypertension.
  
  
  METHODS
  We performed a case-control study of TNFRSF4 in two independent population.
  
  
  RESULTS
  Extensive investigation of single nucleotide polymorphisms of the entire gene suggested that it resided in one linkage disequilibrium block, and four single nucleotide polymorphisms in the 5' flanking region sufficiently represented major haplotypes. In the combined population, the frequency of the most frequent haplotype, C-C-A-A, was significantly lower (P = 8.07 x 10(-5)) and that of the second most frequent haplotype, C-T-G-A, was significantly higher (P = 6.07 x 10(-4)) in hypertensive subjects than in control subjects. This difference was observed only in female patients. The C-T-G-A haplotype showed a lower promoter activity than other haplotypes, suggesting a relationship with disease susceptibility.
  
  
  CONCLUSIONS
  Our results suggest that TNFRSF4 is a female-specific susceptible gene for essential hypertension.
authors.affiliation: Department of Public Health, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Mashimo
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Kazuko
authors.initials: K
authors.lastname: Hatori
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Michiko
authors.initials: M
authors.lastname: Yamada
authors.forename: Norio
authors.initials: N
authors.lastname: Takahashi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Makita
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakayama
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Hirawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imai
authors.forename: Akira
authors.initials: A
authors.lastname: Hata
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007564:Japan; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053262:Receptors, OX40 / Q000235:genetics*; D012737:Sex Factors
chemical_list: D053262:Receptors, OX40; C505716:TNFRSF4 protein, human