TITLE:
Polymorphism of Renalase Gene in Patients of Chronic Kidney Disease
AUTHORS:
Ravinder Singh Ahlawat, Swapan Gupta, Seema Kapoor, Premashish Kar
KEYWORDS:
Chronic Kidney Disease (CKD); Hypertension; Hypertensive Nephrosclerosis; Renalase; Single Nucleotide Polymorphisms (SNP); End Stage Renal Disease (ESRD)
JOURNAL NAME:
Open Journal of Nephrology,
Vol.2 No.4,
January
2,
2013
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.