Abstract
BackgroundDiabetic nephropathy is a global common cause of chronic kidney disease and end-stage renal disease. A lot of research has been conducted in biomedical sciences, which has enhanced understanding of the pathophysiology of diabetic nephropathy and has expanded the potential available therapies. An increasing number of evidence suggests that genetic alterations play a major role in development and progression of diabetic nephropathy. This systematic review was focused on searching an association between Arg913Gln variation in SLC12A3 gene with diabetic nephropathy in individuals with Type 2 Diabetes and Gitelman Syndrome.MethodsAn extensive systematic review of the literature was completed using PubMed, EBSCO and Cochrane Library, from their inception to January 2018. The PRISMA guidelines were followed and the search strategy ensured that all possible studies were identified to compile the review. Inclusion criteria for this review were: 1) Studies that analyzed the SLC12A3 gene in individuals with Type 2 Diabetes and Gitelman Syndrome. 2) Use of at least one analysis investigating the association between the Arg913Gln variation of SLC12A3 gene with diabetic nephropathy. 3) Use of a case–control or follow-up design. 4) Investigation of type 2 diabetes mellitus in individuals with Gitelman’s syndrome, with a history of diabetic nephropathy.ResultsThe included studies comprised 2106 individuals with diabetic nephropathy. This review shows a significant genetic association in most studies in the Arg913Gln variation of SLC12A3 gene with the diabetic nephropathy, pointing out that the mutations of this gene could be a key predictor of end-stage renal disease.ConclusionsThe results showed in this systematic review contribute to better understanding of the association between the Arg913Gln variation of SLC12A3 gene with the pathogenesis of diabetic nephropathy in individuals with T2DM and GS.
Highlights
Diabetic nephropathy is a global common cause of chronic kidney disease and end-stage renal disease
This review shows a significant genetic association in most studies in the Arg913Gln variation of Solute carrier family 12 member 3 (SLC12A3) gene with the diabetic nephropathy, pointing out that the mutations of this gene could be a key predictor of end-stage renal disease
The results showed in this systematic review contribute to better understanding of the association between the Arg913Gln variation of SLC12A3 gene with the pathogenesis of diabetic nephropathy in individuals with Type 2 diabetes mellitus (T2DM) and Gitelman Syndrome (GS)
Summary
Diabetic nephropathy is a global common cause of chronic kidney disease and end-stage renal disease. Dysfunction in NCC could be one of the main causes through which insulin resistance in T2DM-individuals leads to chronic hyperglycaemia state and to diabetic nephropathy risk [32, 33] This assumption is supported by: (a) it has been suggested that most of alterations in SLC12A3 gene are inactivating mutations that impair gene transcription or translation in patients with T2DM and GS [33, 34], (b) This mutational damage would lead to a truncated/alterated NCC cotransporter polypeptide with a loss function causing impaired reabsorption of sodium chloride, potassium and magnesium in the DCT (see Fig. 2) [38, 39], (c) both hypokalaemia as well as hypomagnaesemia have been related to cause insulin secretion abnormalities [33, 40].
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