Polymorphisms of genes of the cardiac calcineurin pathway and cardiac hypertrophy

Poirier, O. et al. (2003) Polymorphisms of genes of the cardiac calcineurin pathway and cardiac hypertrophy. European Journal of Human Genetics, 11, pp. 659-664. (doi: 10.1038/sj.ejhg.5201023)

Abstract

The study investigated the role of genetic polymorphisms in four genes of the calcineurin pathway on cardiac hypertrophy and dilated cardiomyopathy. The cardiac calcineurin pathway has been suggested to play a role in the development of cardiac hypertrophy in response to a number of physiological and pathological stimuli. Calcineurin, a heterodimeric protein composed of a catalytic and a regulatory subunit, activates the nuclear factor NFATC4 which after translocation to the nucleus associates with the transcription factor GATA4 to activate several cardiac genes involved in hypertrophic response. We have screened the genes encoding the four major components of the heart calcineurin pathway in 95 individuals and identified 27 polymorphisms. These polymorphisms were investigated in 400 selected subjects obtained from a population-based study (LOVE) in relation to echocardiographic parameters. A Gly/Ala substitution at position 160 of the NFATC4 protein (G160A) was associated with left ventricular mass and wall thickness (P=0.02 and 0.006, respectively, GA+AA vs GG), the minor allele (Ala) being associated with lower mean values of these parameters. The other polymorphisms identified by the gene screen were not associated with cardiac phenotypes. For the G160A polymorphism in NFATC4, genotype frequencies were compared between patients with dilated cardiomyopathy and controls obtained from the CARDIGENE Study. Allele A carriers were less frequent in the patient than in the control group (P=0.04). Although the strength of the associations was rather weak, these observations raise the hypothesis that the G160A polymorphism of the NFATC4 gene plays a role in the development of human cardiac hypertrophy.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McDonagh, Dr Theresa and Dargie, Professor Henry
• Authors: Poirier, O., Nicaud, V., McDonagh, T., Dargie, H.Z., Desnos, M., Dorent, R., Roizes, G., Schwartz, K., Tiret, L., Komajda, M., and Cambien, F.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: European Journal of Human Genetics
• Publisher: Nature Publishing Group
• ISSN: 1018-4813