Effects of genetic variation in adducin on left ventricular diastolic function as assessed by tissue Doppler imaging in a Flemish population

Tatiana Kuznetsova, Lorena Citterio, Lieven Herbots, Simona Delli Carpini, Lutgarde Thijs, Nunzia Casamassima, Tom Richart, Robert H. Fagard, Giuseppe Bianchi, Jan A. Staessen

Research output: Contribution to journalArticle

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). CONCLUSION: 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.

Original languageEnglish
Pages (from-to)1229-1236
Number of pages8
JournalJournal of Hypertension
Volume26
Issue number6
DOIs
Publication statusPublished - Jun 2008

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Keywords

  • Adducing
  • Echocardiography
  • General population
  • Mitral annular tissue velocity
  • Tissue Doppler imaging

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

Cite this

Kuznetsova, T., Citterio, L., Herbots, L., Carpini, S. D., Thijs, L., Casamassima, N., Richart, T., Fagard, R. H., Bianchi, G., & Staessen, J. A. (2008). Effects of genetic variation in adducin on left ventricular diastolic function as assessed by tissue Doppler imaging in a Flemish population. Journal of Hypertension, 26(6), 1229-1236. https://doi.org/10.1097/HJH.0b013e3282f97dcd