A Functional Polymorphism in Renalase (Glu37Asp) Is Associated with Cardiac Hypertrophy, Dysfunction, and Ischemia: Data from the Heart and Soul Study

• Published in: PloS one Vol. 5; no. 10; p. e13496
• Main Authors: Farzaneh-Far, Ramin, Desir, Gary V., Schiller, Nelson B., Whooley, Mary A.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.10.2010; Public Library of Science (PLoS)
• Subjects: Adenine; Aged; Amino acids; Angina pectoris; Aspartic Acid - chemistry; Authorship; Beta blockers; Cardiomegaly - genetics; Cardiovascular disease; Cardiovascular Disorders; Catecholamines; Clinical trials; Coronary artery; Coronary artery disease; Coronary heart disease; Coronary vessels; Deoxyribonucleic acid; DNA; Echocardiography; Enzymatic activity; Enzymes; Female; Flavin-adenine dinucleotide; Gene polymorphism; Genetic aspects; Genetic testing; Genetics and Genomics; Genotypes; Glutamic Acid - chemistry; Health risk assessment; Heart; Heart attacks; Heart diseases; Heart failure; Heart hypertrophy; Hemodialysis; Human subjects; Humans; Hypertrophy; Ischemia; Kidney diseases; Male; Medicine; Middle Aged; Monoamine Oxidase - chemistry; Monoamine Oxidase - genetics; Mortality; Myocardial Ischemia - genetics; NADH; Nephrology; Nervous system; Nicotinamide adenine dinucleotide; Patients; Polymorphism; Polymorphism, Single Nucleotide; Prospective Studies; Purines; Quality of life; R&D; Research & development; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Structure-function relationships; Ventricle; United States > US; San Francisco Bay; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0013496

Renalase is a soluble enzyme that metabolizes circulating catecholamines. A common missense polymorphism in the flavin-adenine dinucleotide-binding domain of human renalase (Glu37Asp) has recently been described. The association of this polymorphism with cardiac structure, function, and ischemia has not previously been reported. We genotyped the rs2296545 single-nucleotide polymorphism (Glu37Asp) in 590 Caucasian individuals and performed resting and stress echocardiography. Logistic regression was used to examine the associations of the Glu37Asp polymorphism (C allele) with cardiac hypertrophy (LV mass>100 g/m2), systolic dysfunction (LVEF<50%), diastolic dysfunction, poor treadmill exercise capacity (METS<5) and inducible ischemia. Compared with the 406 participants who had GG or CG genotypes, the 184 participants with the CC genotype had increased odds of left ventricular hypertrophy (OR = 1.43; 95% CI 0.99-2.06), systolic dysfunction (OR = 1.72; 95% CI 1.01-2.94), diastolic dysfunction (OR = 1.75; 95% CI 1.05-2.93), poor exercise capacity (OR = 1.61; 95% CI 1.05-2.47), and inducible ischemia (OR = 1.49, 95% CI 0.99-2.24). The Glu37Asp (CC genotype) caused a 24-fold decrease in affinity for NADH and a 2.3-fold reduction in maximal renalase enzymatic activity. A functional missense polymorphism in renalase (Glu37Asp) is associated with cardiac hypertrophy, ventricular dysfunction, poor exercise capacity, and inducible ischemia in persons with stable coronary artery disease. Further studies investigating the therapeutic implications of this polymorphism should be considered.