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Page 2 of 10 Purkait et al. Vessel Plus 2018;2:19 I http://dx.doi.org/10.20517/2574-1209.2018.16

Conclusion: Thus, it is concluded that a genetic variant of the REN gene should have a significant impact on the onset of
type 2 diabetic nephropathy.

Keywords: Single nucleotide polymorphism, type 2 diabetes mellitus, nephropathy, Indian population

INTRODUCTION
Nephropathy is related to damage or disease of the kidney. Diabetic nephropathy is impairment to the
kidney caused by hyperglycemia. In severe cases the kidney can fail. The kidneys filter waste from blood
through its capillaries. Diabetes resulting in high blood sugar can destroy these tiny blood vessels (American
Diabetes Association). Renal failure or kidney disease in diabetes is intervened by various biochemical
pathways such as renin-angiotensin-aldosterone system (RAAS) , aldose reductase-polyol , di-acyl
[1,2]
[3]
glycerol-protein kinase C , advanced glycosylation-end products (AGE) and hexosamine pathway . The
[7]
[4]
[5,6]
RAAS regulates blood pressure and water balance. Renin is secreted by the kidneys when blood pressure
is low and it stimulates the production of angiotensin (Ang). Ang causes blood vessels to constrict, which
results in high blood pressure. Experimental and clinical evidence recommend that the RAAS is a controller
of kidney functions and is proposed to play an important role in the progression of nephropathy in type 2
diabetes mellitus [8-10] .
Renin is a component of the RAAS and it is a protein containing 406 amino acids together with a pre segment
carrying 20-23 and a pro segment of 43-47 amino acids [11-14] . In a number of steps, pro-renin is generated in
the juxtaglomerular cells of the kidney by the elimination of 23 amino acids from C-terminus of prepro-
renin, and is later converted into mature renin by removal of N-terminal fragment of pro-renin [12,14] . Renin,
an aspartyl protease, is encoded by the REN gene and is mapped to 1q25-q32 by in situ hybridization . It
[15]
spans 12.5 kb in length of DNA and contains 8 introns and encodes 10 exons . It cleaves angiotensinogen
[16]
[17]
and it converts it to Ang I after which, Ang I-converting enzyme (ACE) transforms it into Ang II, a potent
vasoconstrictor. The concentrations of angiotensinogen circulating in the blood is abundant and perhaps
more than 1000 times in excess of plasma Ang I and Ang II concentrations . Although with exception of
[18]
some species, activity of renin thus is a key factor for the determination of the rate of Ang I formation in the
plasma from enormous supplies of circulating angiotensinogen [19,20] . Therefore, even small relative changes
in the rates of Ang I formation perhaps lead to a large absolute difference in the circulating concentrations
of Ang II. It is well known that renin is synthesized and stored in substantial quantities in the granules
of juxtaglomerular cells and is released in response to various stimuli [20,21] . Thus, large changes in plasma
renin levels can rapidly changes the generation of Ang I. Therefore the polymorphism in the promoter
region of REN gene may be of great significance in the changes Ang I. Ang I is easily converted to Ang II
because the widespread presence of Ang converting enzyme on endothelial cells of many vascular beds
including lung [19,20,22] . The resultant increases in plasma Ang II exert powerful actions throughout the body
through activation of AGTR1 receptors [20,23] . In this context renin is also an important regulator of blood
pressure and electrolyte balance. Individuals with REN polymorphisms have been associated with high
blood pressure [24,25] , susceptibility to hypertension [26-28] and end-stage renal disease .
[29]

Keeping the existing body of knowledge in view, the aim of the present study was to investigate the
distribution of genotype, allele frequency of REN gene polymorphism and its relationship with type 2
diabetic nephropathy patients in an Eastern Indian population.

METHODS
Subjects
Patients were recruited from registered patients list of two participating medical institutions of Kolkata,
West Bengal. A standardized protocol was implemented to obtain data from each of the study participants.