Genetic variants of renin on the prevalence of diabetic nephropathy

Abstract

Aim: Renin, a component of the Renin-Angiotensin-Aldosterone System (RAAS), is produced in the juxtaglomerular cells of the kidney. It is an important factor for the regulation of blood pressure and electrolyte balance and encoded by the REN gene. Recent studies suggest that the RAAS is a regulator of kidney functions. Individuals with REN variants have been associated with high blood pressure. We substantiated the hypothesis that genetic variants of REN gene have significant association with prevalence of nephropathy and in the development of nephropathy in type 2 diabetes mellitus (T2DM). Methods: We enrolled to the study 718 consecutive subjects who were registered patients in two individual hospitals in Kolkata city, India. They consisted of 246 (34.26%) T2DM patients without nephropathy cases, 168 (23.40%) type 2 diabetes with nephropathy cases (T2DNH) and 304 (42.34%) healthy controls. Genotypes were assayed with genomic DNA for two known variants of the REN gene, i.e., rs16853055 and rs41317140 using sequencing methods. Results: Association between the REN gene variants and prevalence of T2DM and T2DNH was tested. A significant association of T2DNH and variant rs41317140 was obtained and it was evident that the rs41317140 (C>T) shows a significant difference between T2DM and T2DNH (x 2 = 4.92; P = 0.03; OR = 0.6162; 95% CI: 0.4006-0.948). The results from the multiple model test that additive model predicted the association at genotype level and shows a significant difference between T2DM and T2DNH (OR = 0.6067; P = 0.03). There was no significant association between T2DNH or T2DM and variant rs16853055. 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.

Diabetes and Renin-Angiotensin-Aldosterone System: Pathophysiology and Genetics

“…Meta-analysis performed by Xu et al demonstrated association of allelic frequency as well as co-dominant homozygous and recessive models of inheritance with regard to −344 T/C polymorphism within promoter region of CYP11B2 gene with the increased risk of diabetic nephropathy [112]. Similar association was observed by Purkait et al [113] in Indian population. Promoter regions play important regulatory roles in gene transcription followed by formation of a functional protein through translation.…”

“…Previous studies reported association of renin gene polymorphisms with number of non-communicable diseases including diabetic nephropathy [89], increased risk of vascular complications [90], plasma renin activity [91], susceptibility to hypertension in a variety of ethnic groups [92][93][94][95], T2D [96] with inconsistent results [97][98][99]. Few studies did not find any significant association of renin rs16853055 with diabetes and diabetic nephropathy diseases [100,101] while Purkait et al [102] found an association of this variant with diabetic nephropathy in Indian population along with strong linkage disequilibrium with rs16853055. On the other hand, Deinum et al reported weak association of renin gene polymorphism present in the first intron (involved in the regulation of transcription of renin) with diabetic nephropathy [89,103].…”

Genetic Appraisal of RAAS-Associated SNPs: REN (rs16853055), AGT (rs3789678) and ACE (rs4305) in Preeclamptic Women Living with HIV Infection

“…There is a paucity of data on REN ( rs16853055 ) polymorphism. Purkait et al showed that this polymorphism had no association with diabetic nephropathy in participants of Indian ancestry [ 93 ]. Since this SNP has not yet been analysed within the realm of HDP co-morbid with HIV in sub-Saharan Africa, particularly South Africa, extensive research is required to enhance our understanding of its role as a genetic contributor to disease development as well as its associated functional properties.…”