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Gall bladder cancer (GBC) is a relatively rare but highly fatal disease, particularly in North India. The angiotensin I-converting enzyme ( ACE) insertion/deletion (I/D) gene polymorphism influences serum angiotensin II action, which has been associated with various malignancies. This population-based case–control study was undertaken to examine the potential association of ACE I/D variation with GBC in a North Indian population. Genotypes and allelic frequencies of the ACE I/D polymorphism (rs4646994) were determined for 233 GBC patients and 260 cancer-free controls randomly selected from the population using polymerase chain reaction. Odds ratio (OR) and 95% confidence interval were calculated in multivariate logistic regression analysis for the association of ACE polymorphism with GBC. The ACE I/D polymorphism was found to be nonsignificantly associated with an overall increased risk of GBC (OR = 1.04 and 1.38 for I/D and D/D genotypes, respectively; ptrend = 0.375). The increased risk was predominant significantly in female cohort and nonsignificantly in GBC patients with gallstone status (OR = 1.63; p = 0.039 and OR = 1.37; p = 0.187, respectively). In summary, ACE I/D polymorphism may alter the susceptibility to GBC, especially in women. [ABSTRACT FROM AUTHOR]

Increased vascular endothelial growth factor (VEGF) production promotes enhanced endothelial permeability, enhanced leukocyte migration into the allograft, thereby leading to a clinically recognized rejection episode. Interleukin-18 (IL-18), a potent proinflammatory cytokine, may also be involved in mechanisms of kidney allograft rejection. The present study was, therefore, undertaken to investigate the association of functional polymorphisms in VEGF (2578C>A, 1154A>G) and IL-18 (607C>A, 137G>C) genes with risk of allograft rejection in renal transplant recipients of North India. Two hundred renal transplant recipients, 150 matched recipients-donors, and 200 unrelated healthy individuals were genotyped by amplification refractory mutation specific polymerase chain reaction and by polymerase chain reaction-restriction fragment length polymorphism. Variant allele VEGF 1154A>G ( p = 0.56; odds ratio [OR] = 1.32) and variant allele ( p = 0.004, OR = 1.54) and variant genotype ( p = 0.007, OR = 3.26) of IL-18 607C>A, GC of IL-18 137G>C ( p = 0.043, OR = 0.63) were significantly different in healthy individuals as compared with the patients with renal transplant. When 114 nonrejectors were compared with 36 rejectors (150 recipients) for association with allograft rejection, significant association was observed in heterozygous genotype of VEGF 2578C>A ( p = 0.033), VEGF 1154A>G ( p = 0.024). In IL-18 137G>C, CC genotype, C allele showed protective association with allograft rejection. Kaplan-Meier analysis indicated a higher mean time for first rejection episode in CA genotype carriers (31 months) as compared with AA (29 months) for VEGF 2578C>A (log p = 0.035). In VEGF, the haplotypes A-A and A-G (2578-1154) were associated with reduced risk and in IL-18 607A-137G, they were associated with high risk for allograft rejection. This observation suggests these polymorphisms are an ideal marker for prediction of pretransplant allograft outcome. [ABSTRACT FROM AUTHOR]