Role Of Il-6 (-174 G/C) Polymorphism And Renal Biopsy, Clinical & Immunoinflammatory Markers In Pathogenesis Of Type 2 Diabetic Nephropathy

Background: Diabetic nephropathy (DN) is the leading cause of chronic kidney failure worldwide and most significant in terms of morbidity and mortality in ∼40% of Type2 DN patients. Type2 DN is frequently associated with renal injury. Increased glomerular interstitial infiltration of macrophages/ monocytes inducing inflammation and synthesis of proinflammatory cytokines such as interleukin-6 (IL-6). Interleukin-6 is a pleiotropic cytokine, playing a pivotal role in T2DN and its polymorphic gene variants modulate cellular response & to inter individual variation among T2DN patients. Objective: To evaluate the role of polymorphic variant of IL- 6 (-174 G/C), involved in pathogenesis of T2DN, in association with the pathological analysis of renal biopsy, clinical & immunoinflammatory markers. Methods: 220 patients with T2DN and an equal number of age and gender matched controls were recruited. Blood samples were collected from Nizam’s Institute of Medical Sciences (NIMS), Hyderabad. Informed written consent was obtained from all the subjects. Renal biopsy analysis was analysed by TEM microscopy, obtained from the hospital. Clinical and immunoinflammatory levels were estimated based on the standardized protocols. Genotyping of IL- 6 (-174 G/C) polymorphism was done by PCR- RFLP method. Results: IL-6 (-174 G/C) polymorphism of GC & CC genotype was found to be conferring 18.96- & 9.03-fold risk in codominant, dominant and recessive models with T2DN. Mean biopsy associated with histopathological changes increased levels of clinical and immunoinflammatory markers in T2DN at p<0.01. Conclusion: Our data suggest the importance of GC & CC genotype of IL- 6 (-174 G/C) polymorphism as a risk factor for susceptibility to T2DN. Pathological changes in renal biopsy, clinical and immunoinflammatory markers associated with T2DN.