title: Effects of genetic variation in adducin on left ventricular diastolic function as assessed by tissue Doppler imaging in a Flemish population.
abstract: BACKGROUND
  We investigated the possible association between left ventricular diastolic function and the ADD1 Gly460Trp and ADD3 IVS11 +386A>G polymorphisms alone and in combination.
  
  
  METHODS
  In a family-based population study (473 subjects; 50.5% women; mean age 50.5 years), we measured early (Ea) and late (Aa) diastolic peak velocities of the mitral annulus by tissue Doppler imaging. In multivariate-adjusted analyses, we investigated phenotype-genotype associations, while accounting for confounders and family structure.
  
  
  RESULTS
  Lateral Ea/Aa ratio was higher in ADD1 Trp allele carriers than in GlyGly homozygotes (1.51 vs. 1.40; P = 0.005) and was lower in ADD3 A allele carriers than in GG homozygotes (1.42 vs. 1.55; P = 0.005). The effects of ADD1 on the lateral Ea and Ea/Aa weakened with older age (P < 0.05). The best fitting model for lateral Ea and Ea/Aa included ADD1, ADD3, and the three-way interaction term of both genes with age. Below the age of 50 years, the lateral Ea/Aa ratio was higher in ADD1 Trp allele carriers than in GlyGly homozygotes (1.91 vs. 1.73; P = 0.006), particularly in the presence of ADD3 GG homozygosity (2.46 vs. 1.80; P = 0.0008). In older subjects, these phenotype-genotype associations were not significant (P > 0.20). Transmission of the ADD1 Trp allele to offspring was associated with higher lateral Ea (+0.91; P = 0.026) and Ea/Aa ratio (+0.23; P = 0.0008).
  
  
  CONCLUSIONS
  Our population-based study demonstrated that left ventricular diastolic relaxation is modulated by genetic variation in ADD1 and ADD3. This association was more prominent in younger subjects in whom longstanding environmental factors and ageing are less likely to mask genetic effects.
authors.affiliation: Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kuznetsova
authors.forename: Lorena
authors.initials: L
authors.lastname: Citterio
authors.forename: Lieven
authors.initials: L
authors.lastname: Herbots
authors.forename: Simona Delli
authors.initials: SD
authors.lastname: Carpini
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Thijs
authors.forename: Nunzia
authors.initials: N
authors.lastname: Casamassima
authors.forename: Tom
authors.initials: T
authors.lastname: Richart
authors.forename: Robert H
authors.initials: RH
authors.lastname: Fagard
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bianchi
authors.forename: Jan A
authors.initials: JA
authors.lastname: Staessen
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D001530:Belgium; D001783:Blood Flow Velocity; D002148:Calmodulin-Binding Proteins / Q000235:genetics* / Q000502:physiology; D003971:Diastole / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000502:physiology; D011110:Polymorphism, Genetic; D016277:Ventricular Function, Left / Q000502:physiology*; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D000099291:Adducins; C102021:ADD3 protein, human