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Page 6 of 10 Purkait et al. Vessel Plus 2018;2:19 I http://dx.doi.org/10.20517/2574-1209.2018.16

Table 4. Logistic regression analysis of SNPsrs16853055 (C >A) and rs41317140 (C >T) of RENIN gene among the study groups
SNP Study groups Additive model Dominant model Recessive model
OR L95 U95 P value OR L95 U95 P value OR L95 U95 P value
rs16853055 CON vs. T2DM 1.18 0.84 1.67 0.32 1.12 0.77 1.62 0.55 3.77 0.75 18.87 0.11
CON vs. T2DNH 0.78 0.51 1.19 0.25 0.73 0.47 1.15 0.18 1.81 0.25 13.03 0.55
T2DM vs. T2DNH 0.67 0.44 1.02 0.06 0.65 0.41 1.04 0.07 0.48 0.09 2.41 0.37
rs41317140 CON vs. T2DM 1.25 0.88 1.77 0.20 1.19 0.81 1.74 0.36 3.77 0.75 18.87 0.11
CON vs. T2DNH 0.74 0.47 1.16 0.19 0.76 0.48 1.20 0.24 0.00 0.00 inf 0.99
T2DM vs. T2DNH 0.61 0.39 0.94 0.03* 0.63 0.39 1.02 0.05 0.00 0.00 inf 0.99
SNP: single nucleotide polymorphism; A1: code for allele 1 ( the more rare or “minor” allele based on the entire sample frequencies); A2:
code for allele 2 ( the more common or “major” allele); CON: control group; T2D: over all type 2 diabetes with and without nephropathy
group; T2DM: type 2 Diabetes without nephropathy group ; T2DNH: type 2 diabetes with nephropathy who are on hemodialysis group; F_
A: frequency of minor allele in affected individuals (case); F_U: frequency of minor allele in unaffected individuals (control); CHISQ: Chi-
squared value for allelic association (with 1 df); P: the asymptotic P-value for chi-square test; OR: odds ratio; L95: lower bound of the 95%
confidence; U95: upper bound of the 95% confidence; *Significant

the kidney is unique, because it contains all the elements of the RAAS with compartmentalization in the
interstitial networks and tubules as well as intracellular accumulation . In this regard, the adrenal glands
[54]
along with the kidneys are distinctive because of their tissue concentrations of Ang II, which are much higher
than can be explianed by the concentrations transported by the arterial blood flow . There is considerable
[55]
evidence that the major fraction of Ang II present in renal tissues is greater locally from Ang delivered to the
kidney as well as from angiotensinogen locally produced by proximal tubule cells [56,57] . Renin secreted by the
juxtaglomerular apparatus cells and delivered to the renal interstitium and vascular compartment appear to
be a most powerful controller for producing Ang I from Ang [58,59] . To regulate the production of Ang II, renin
is most important, because once Ang I is formed, conversion readily occurs as there are abundant amounts
of Ang converting enzyme in circulation. In this regard the genetic variants of REN gene may have a vital
[54]
role in the regulation of the gene expression as well as the regulation of Ang II production.

Previous findings show that renin gene polymorphism have been associated with diabetic nephropathy [39,60-62] ,
increased risk of vascular complications [25,63] , plasma renin activity (PRA) , susceptibility to hypertension
[44]
in a variety of ethnic groups [24,25,27,64,65] , T2DM [66,67] , and CRI although often with inconsistent results [69,70] .
[68]
A few studies have reported that the renin rs4131714 (-4063C/T) a promoter variant has no association with
DN [39,68,71] , whereas the present study found a positive association between rs4131714 (-4063C/T) and T2DNH
(P = 0.02655), which shows high linkage disequilibrium (LD) with rs16853055 (D’ = 0.936; LOD = 82.03;
r2 = 0.823), [Figure 3]. However, the rs16853055 did not show any significant association with diabetes and
diabetic nephropathy diseases. Deinum et al. also reported weak association of REN gene (Bgl I RFLP)
[39]
polymorphism in the first intron with diabetic nephropathy along with increased level of plasma renin. The
first intron is involved in the renin gene transcription regulation and therefore Bgl I RFLP may have some
[72]
contribution in this regard. Likewise the renin rs4131714 (-4063C/T) promoter variant may also have some
regulatory function in the expression of prorenin or renin which is subject to further study. Though we have
not measured the level of plasma prorenin or renin which is beyond our scope, but one can illustrate that
area. In any future study one can also investigate the precise role of rs16853055 (-3879C/A) polymorphism in
connection with diabetic nephropathy, as it shows high linkage disequilibrium with rs4131714 (-4063C/T).

Genetic sketching of the functional genes helps to explore a particular disease as well as helps to recognize
the tendency of that disease within a particular population that may eventually be of support to the doctors
for recommending personalized medicine.

The present study has to be taken under consideration within its limitations; that it was limited to a specific
ethnic group (Eastern Indian Bengali population). A larger study from different ethnic groups will be needed
to confirm for any contribution of renin gene polymor-phism to T2DM complications for development of