title: Epistatic interaction between alpha- and gamma-adducin influences peripheral and central pulse pressures in white Europeans.
abstract: BACKGROUND
  Adducin is a membrane skeleton protein consisting of alpha- and beta- or alpha- and gamma-subunits. Mutations in alpha- and beta-adducin are associated with hypertension. In the European Project on Genes in Hypertension, we investigated whether polymorphisms in the genes encoding alpha-adducin (Gly460Trp), beta-adducin (C1797T) and gamma-adducin (A386G), alone or in combination, affected pulse pressure (PP), an index of vascular stiffness.
  
  
  METHODS
  We measured peripheral and central PP by conventional sphygmomanometry and applanation tonometry, respectively. We randomly recruited 642 subjects (162 nuclear families and 70 unrelated individuals) from three European populations. In multivariate analyses, we used generalized estimating equations and the quantitative transmission disequilibrium test.
  
  
  RESULTS
  Peripheral and central PP averaged 46.1 and 32.6 mmHg, respectively. Among carriers of the alpha-adducin Trp allele, peripheral and central PP were 5.8 and 4.7 mmHg higher in gamma-adducin GG homozygotes than in their AA counterparts, due to an increase in systolic pressure. gamma-Adducin GG homozygosity was associated with lower urinary Na/K ratio among alpha-adducin Trp allele carriers and with higher urinary aldosterone excretion among alpha-adducin GlyGly homozygotes. Sensitivity analyses in founders and offspring separately, and tests based on the transmission of the gamma-adducin G allele across families, confirmed the interaction between the alpha- and gamma-adducin genes.
  
  
  CONCLUSIONS
  In alpha-adducin Trp allele carriers, peripheral and central PP increased with the gamma-adducin G allele. This epistatic interaction is physiologically consistent with the heterodimeric structure of the protein and its influence on transmembranous sodium transport.
authors.affiliation: Department of Internal Medicine and Gerontology, Medical College, Jagiellonian University, Cracow, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Cwynar
authors.forename: Jan A
authors.initials: JA
authors.lastname: Staessen
authors.forename: Milena
authors.initials: M
authors.lastname: Tichá
authors.forename: Tim
authors.initials: T
authors.lastname: Nawrot
authors.forename: Lorena
authors.initials: L
authors.lastname: Citterio
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kuznetsova
authors.forename: Wiktoria
authors.initials: W
authors.lastname: Wojciechowska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Stolarz
authors.forename: Jan
authors.initials: J
authors.lastname: Filipovský
authors.forename: Kalina
authors.initials: K
authors.lastname: Kawecka-Jaszcz
authors.forename: Tomasz
authors.initials: T
authors.lastname: Grodzicki
authors.forename: Harry A
authors.initials: HA
authors.lastname: Struijker-Boudier
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Thijs
authors.forename: Luc M
authors.initials: LM
authors.lastname: Van Bortel
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bianchi
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000652:urine; D012044:Regression Analysis; D012964:Sodium / Q000652:urine; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D011188:Potassium; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D000099291:Adducins