Abstract
Introduction: Chronic kidney disease (CKD) is an important public health problem. Early detection and treatment is a key factor for prevention of its complications. Hypertensive nephrosclerosis is a subtype of CKD which has a poor correlation between hypertension and development of nephropathy, implying role of genetic factors or epigenetic factors. The knowledge regarding genetic factors is limited. Renalase is a novel hormone with its gene on chromosome 10, which secretes flavin adenine dinucleotide dependent amine oxidase. Renalase metabolizes circulating catecholamines and modulates blood pressure and cardiac function. Recently, two single nucleotide polymorphisms of renalase gene rs2576178 GG and rs2296545 CC have been linked to essential hypertension. The SNPrs2296545 CC is also shown to be associated with cardiac hypertrophy, dysfunction and ischemia. The association of these two single nucleotide polymorphisms with hypertensive nephrosclerosis has not been investigated. Methods: We designed a case-control study to investigate whether the two known renalase gene polymorphisms rs2576178 and rs2296545 are associated with CKD particularly hypertensive nephrosclerosis. We genotyped these two polymorphisms in 287 subjects from North Indian population (106 CKD cases and 181 controls). Results: Comparison shows that subjects with hypertensive nephrosclerosis had higher frequencies of rs2296545 Callele than the healthy controls (0.63 versus 0.47, p 0.02). The odds ratio for rs2296545 CC genotype in hypertensive nephrosclerosis were 2.55 (95% CI, 1.03 to 6.42; p = 0.02) (CC versus GG) and 2.11(95% CI, 1.01 to 4.42; p = 0.03) (CC versus CG + GG) compared to controls. Conclusion: These findings may provide novel insight into the role of additional genomic regions as susceptibility gene in the pathophysiology of hypertensive nephrosclerosis. Further, to account for geoethnic variation, studies on heterogeneous populations involving a larger sample size are required. The correlation between this structural change and actual levels of the enzyme or the activity are required to strengthen this association as well as to be clinically applicable.
Highlights
Chronic kidney disease (CKD) is an important public health problem
We designed a case-control study to investigate whether the two known renalase gene polymorphisms rs2576178 and rs2296545 are associated with CKD hypertensive nephrosclerosis
We studied whether the polymorphism in renalase gene is associated with CKD in general or with hypertensive nephropathy or nephrosclerosis, possibly due to following reasons: 1) Hypertension is common in patients with chronic renal disease
Summary
Chronic kidney disease (CKD) is an important public health problem. Early detection and treatment is a key factor for prevention of its complications. Methods: We designed a case-control study to investigate whether the two known renalase gene polymorphisms rs2576178 and rs2296545 are associated with CKD hypertensive nephrosclerosis. We genotyped these two polymorphisms in 287 subjects from North Indian population (106 CKD cases and 181 controls). It is difficult to assess whether this predisposition is due to a specific genetic susceptibility to renal damage, or to other comorbid conditions generally accepted to have poly- or oligo-genetic components, like hypertension, diabetes or atherosclerosis Still, this observation has launched the search for nephropathy susceptibility genes. A number of factors like renovascular disease, hypertension, recurrent urinary tract infection and obstructive uropathy are implicated for CKD in ageing population [5,6]
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