Genotypic Analysis of COL4A1 Gene in Diabetic Nephropathy and Type 2 Diabetes Mellitus Patients: A Comparative Genetic Study.

Diabetic nephropathy (DN) is specified by microalbuminuria, glomerular lesions, and renal fibrosis leading to end-stage renal disease. The pathophysiology of DN is multifactorial as a result of gene-environment interaction. Clinical studies suggested that gene mutations affect various pathways involved in DN, including extracellular matrix (ECM). During chronic hyperglycemia, collagen type-4-mediated ECM overproduction occurs, leading to renal fibrosis and DN development. In this study, COL4A1 gene variant rs605143 (G/A) was analyzed in diabetes and DN patients from the study population. We genotyped 386 study subjects, comprising 120 type 2 diabetes mellitus (T2DM) patients, 120 DN, and 146 healthy controls. All study subjects were analyzed for biochemical assays by commercially available kits and genotypic analysis by polymerase chain reaction-restriction fragment length polymorphism and confirmed by Sanger sequencing. Statistical analyses were done using SPSS and GraphPad. Anthroclinicopathological parameters showed a significant association between T2DM and DN. Genotype AA of COL4A1 gene variant rs605143 (G/A) showed a significant association with T2DM and DN compared with controls with 5.87- and 8.01-folds risk, respectively. Mutant allele A also significantly associated with T2DM and DN independently compared with healthy controls with 2.29- and 2.81-time risk in the study population. This study's findings suggested that COL4A1 gene variant rs605143 (G/A) can be used as predictive biomarkers for T2DM and DN independently. However, this gene variant needs to be analyzed in a large sample to explore the shared genetic association between T2DM and DN.

Cancer stem cell in prostate cancer progression, metastasis and therapy resistance.

Prostate cancer (PCa) is the most diagnosed malignancy in the men worldwide. Cancer stem cells (CSCs) are the sub-population of cells present in the tumor which possess unique properties of self-renewal and multilineage differentiation thus thought to be major cause of therapy resistance, disease relapse, and mortality in several malignancies including PCa. CSCs have also been shown positive for the common stem cells markers such as ALDH EZH2, OCT4, SOX2, c-MYC, Nanog etc. Therefore, isolation and characterization of CSCs specific markers which may discriminate CSCs and normal stem cells are critical to selectively eliminate CSCs. Rapid advances in the field offers a theoretical explanation for many of the enduring uncertainties encompassing the etiology and an optimism for the identification of new stem-cell targets, development of reliable and efficient therapies in the future. The emerging reports have also provided unprecedented insights into CSCs plasticity, quiescence, renewal, and therapeutic response. In this review, we discuss the identification of PCa stem cells, their unique properties, stemness-driving pathways, new diagnostics, and therapeutic interventions.