A functional polymorphism in renalase (Glu37Asp) is associated with cardiac hypertrophy, dysfunction, and ischemia: data from the heart and soul study.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Farzaneh-Far
Ramin
R
Division of Cardiology, San Francisco General Hospital, San Francisco, California, United States of America. rfarzanehfar@medicine.ucsf.edu
Desir
Gary V
GV
Na
Beeya
B
Schiller
Nelson B
NB
Whooley
Mary A
MA
D000368:Aged; D001224:Aspartic Acid / Q000737:chemistry*; D006332:Cardiomegaly / Q000235:genetics*; D005260:Female; D018698:Glutamic Acid / Q000737:chemistry*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000737:chemistry / Q000235:genetics*; D017202:Myocardial Ischemia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies
D001224:Aspartic Acid; D018698:Glutamic Acid; D008995:Monoamine Oxidase; C521557:renalase