Renalase gene polymorphisms in patients with type 2 diabetes mellitus with and without hypertension

Abstract

Abstract Background Blood pressure (BP) is acutely regulated by the sympathetic nervous system through the action of vasoactive hormones (epinephrine, norepinephrine, and dopamine). Renalase, a recently discovered enzyme with monoamine oxidase activity is implicated in the degradation of catecholamines with a possible role in BP maintenance and cardiac protection against hypertension (HTN) and cardiovascular (CV) events. Objectives The aim of this study was to identify the potential involvement of renalase gene polymorphisms in patients with type 2 diabetes mellitus (T2DM) with or without HTN in the absence of diabetic nephropathy and to illustrate the role of renalase gene single-nucleotide polymorphisms (rs2576178 and rs10887800) in CV events. Study design This was a cross-sectional study. Patients and methods A total of 180 patients with T2DM attending the diabetes and cardiology clinics of Mansoura Hospital were recruited in the study: 100 patients with T2DM with HTN and 80 patients with T2DM who were normotensive. Further, 50 apparently healthy individuals matched in age and sex were included as a reference group. Clinical and laboratory examinations stressing on symptoms and signs of diabetes and HTN complications and ECG and Holter ECG monitoring stressing on QTc and QTd were performed; BMI, lipograms, microalbumin levels, and serum creatinine levels were also determined. Patients with renal disease, hepatic disease, and heart failure, those with previous or present renal or suprarenal lesions or endocrinopathies, and those with secondary HTN were excluded from the study. Genotype determination for two single-nucleotide polymorphisms (rs2576178 and rs10887800) in the renalase gene was carried out using the PCR method. Results The frequency of the GG allele of rs2576178 and rs10887800 was insignificantly higher in the diabetic hypertensive group than in the diabetic normotensive group. Both diabetic groups showed higher levels of GG alleles than the control group. The frequency of the GA allele of rs2576178 was significantly higher in the diabetic hypertensive group in comparison with the normotensive diabetic group. The allele frequency of G and A alleles of both studied renalases was also higher in the diabetic hypertensive group in comparison with the diabetic normotensive group; however, the differences were insignificant. The genotype distribution and allele frequencies did not show any statistically significant association with BMI, neuropathy, retinopathy, myocardial ischemia, QTc, or QTd. Conclusion The renalase gene can be potentially involved in BP regulation in T2DM. Further large-scale studies on the relationship between renalase and acute coronary syndrome and CV events are warranted.