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.

Polymorphism T81C in H-RAS Oncogene Is Associated With Disease Progression in Imatinib (TKI) Treated Chronic Myeloid Leukemia Patients.

BACKGROUND: Mammalian cells contain three functional RAS proto-oncogenes, known as H-RAS, K-RAS, and N-RAS, which encode small GTP-binding proteins in terms of p21rass. RAS genes have been elucidated as major participants in the development and progression of cancer. A single nucleotide polymorphism (SNP) at H-RAS cDNA position 81 T→C (rs12628) has been found to be associated with the risk of many human cancers like gastrointestinal, oral, colon, bladder and thyroid carcinomas. Therefore, we hypothesized that this polymorphisms in H-RAS could influence susceptibility to chronic myeloid leukemia as well, and we conducted this study to test the hypothesis in Indian population. METHOD: H-RAS polymorphism was studied in 100 chronic myeloid leukemia (CML) patients and 100 healthy controls by restriction fragmentation length polymorphism (RFLP-PCR). Associations between polymorphism and clinicopathological features of CML patients were investigated. RESULTS: In CML patients, the TT, TC and CC genotype frequency was 38%, 61% and 1% respectively, compared to 92%, 8% and 0% in healthy controls respectively. Compared to TT genotype, CT was significantly associated with increased risk of CML (odds ratio (OR): 8.4, P < 0.00001). There was a statistically significant correlation of H-RAS polymorphism with phases (P < 0.0003), molecular response (P < 0.0001), hematological response (P < 0.04) and thrombocytopenia (P < 0.003). However, there was no correlation of this polymorphism found with other clinical parameters. CONCLUSION: H-RAS T81C polymorphism was found to be associated with CML risk and prognosis of CML. These results suggest that C heterozygosis may be considered a potential risk factor for CML development in the North Indian population.

Antihypertensive and antioxidant action of amlodipine and vitamin C in patients of essential hypertension.

The etiology of essential hypertension includes increased oxidative stress. The role of antihypertensive drug amlodipine as an antioxidant and the benefit of addition of vitamin C, an antioxidant to antihypertensive therapy were studied. Forty male patients of essential hypertension were randomly divided into two groups and treated with 5 mg amlodipine. In addition one group also received 1000 mg vitamin C (as two 500 mg tablets) once daily for three months. Although blood pressure decreased in both groups, the systolic blood pressure in patients given vitamin C was less (126.4 +/- 7.47) compared to the other group (130.9 +/- 7.27). A decrease in malondialdehyde, an increase in erythrocyte sodium-potassium adenosine triphosphatase (Na(+) K(+) ATPase) and an increase in the superoxide dismutase levels were observed in both groups. The increase in SOD was statistically more in the patients given vitamin C in addition to amlodipine (0.1717 +/- 0.0150 compared to 0.152 +/- 0.0219 units/100 ml assay). In spite of the known antihypertensive, antioxidant activity, similarity in correcting endothelial dysfunction independently, giving the two drugs together and early introduction of vitamin C perhaps decreases oxidative stress and augments the antioxidant status. This may prevent further vascular damage due to oxidative stress, leading to a better prognosis in essential hypertension patients.