Association of 18bp insertion/deletion polymorphism, at -2549 position of VEGF gene, with diabetic nephropathy in type 2 diabetes mellitus patients of North Indian population.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent multifunctional cytokine which plays a key role in the pathogenesis of diabetic micro-vascular complications. Human VEGF gene is said to be highly polymorphic. Insertion/deletion (I/D) polymorphism of the 18 bp fragment at -2549 position of the promoter region in VEGF gene is said to be of particular interest. The study was aimed to evaluate association of Insertion/deletion (I/D) polymorphism of the 18 bp fragment at -2549 position of the promoter region in VEGF gene, with diabetic nephropathy in type 2 diabetes mellitus. METHODS: This cross sectional study enrolled 40 subjects each of diabetic nephropathy (DN), diabetes mellitus without nephropathy (DM) and normal control subjects. DNA was isolated from peripheral blood leukocytes. Genotyping of the VEGF gene insertion/ deletion (I/D) polymorphism was done by the polymerase chain reaction (PCR) methods. The frequency of VEGF alleles and genotype distribution were compared in diabetic nephropathy, uncomplicated diabetic and control groups. RESULTS: DD genotype and D allele were found to be significantly associated with DN group (p = 0.009 and 0.02 respectively) in comparison to DM group. Also DD genotype conferred significant risk of diabetic nephropathy in DM group (OR = 4.2) (against combined frequency of ID and II genotype) so does D allele 2.09 (against I allele). CONCLUSION: DD genotype and D allele in I/D polymorphism at -2549 position of VEGF gene is associated with increased susceptibility to diabetic nephropathy in north Indian population.

Association of inflammatory cytokines, lipid peroxidation end products and nitric oxide with the clinical severity and fetal outcome in preeclampsia in Indian women.

Preeclampsia is a multisystem disorder associated with maternal hypertension, placental abnormalities and adverse fetal outcomes. The various pathways involved in its etiology include endothelial dysfunction, inflammatory milieu, lipid peroxidation and immunological imbalance. The present study was conducted to evaluate the causative and predictive role of nitric oxide, lipid peroxidation end products (MDA) and inflammatory cytokines (IL-6, TNF-α) in clinical presentation, severity and fetal outcome in preeclampsia. The study population was divided into 3 groups- Non- pregnant females comprising the control population; G1 and G2 groups included normal pregnant and pregnant females with preeclampsia with 50 patients in each group. Nitric Oxide and MDA levels were found to be highest in the preeclamptic patients as compared to other two groups. ROC curve analysis shows the superiority of the inflammatory markers as determinants of severity of preeclampsia which suggests the emerging role of pro inflammatory markers in the various pathological changes in preeclampsia. TNF-α emerged as the best marker in multivariate analysis and thus, has the potential for being used as a marker for PIH. Our study illustrates the multifactorial etiology of preeclampsia involving oxidative stress, proinflammatory milieu and endothelial dysfunction.