Hari Om Singh*, Sushma Jadhav, Dharmesh Samani and Tapan N. Dhole Pages 134 - 150 ( 17 )
Background: Micro RNAs act as a regulatory layer for pharmacogenomics-related gene expression. It could play a role in the efficacy and toxicity of the drug. The SNPs in miRNA genes are linked with different functional consequences.
Methods: Hence, we examined the miR (146a G/C, 149C/T, and 196aC/T) polymorphisms in 34 patients with hepatotoxicity, 123 patients without hepatotoxicity, and 155 healthy controls using a PCRRFLP method.
Results: In patients with hepatotoxicity, miR196aCT genotype and combined genotype GCT showed a risk for hepatotoxicity severity with borderline significance (OR=2.08, P=0.07; OR=2.88, P=0.06). While comparing between patients with hepatotoxicity and healthy controls, the combined genotypes CCC and GCT have shown a susceptibility to hepatotoxicity severity (OR=2.89, P=0.05; OR=2.60, P=0.09). The miR196TT genotype was associated with the individuals of advanced HIV disease stage (OR=3.68, P=0.04). In HIV patients who consumed alcohol and did not have hepatotoxicity, the miR 196aCT genotype showed susceptibility to acquisition of hepatotoxicity with borderline significance (OR=2.36, P=0.06).
Discussion: The miR149TT and 196aTT genotypes showed a risk of acquisition of hepatotoxicity to nevirapine usage among HIV patients without hepatotoxicity (OR=4.19, P=0.07; OR=1.97, P=0.84). In HIV patients with and without hepatotoxicity, the miR 196aCT genotype showed a risk of acquisition of hepatotoxicity and its severity to the combined use of alcohol and nevirapine, respectively (OR=14.18, P=0.08; OR=2.29, P=0.08). In multivariate logistic regression, taking nevirapine, 196aCT genotype had an independent risk factor for hepatotoxicity severity (OR=5.98, P=0.005; OR=2.38, P=0.05).
Conclusion: In conclusion, miR196aC/T polymorphism and combined genotypes GCT and CCC may facilitate the risk for acquisition of hepatotoxicity and its severity.
miRNA polymorphisms, NNRTI regimen, Genetic predisposition, HIV patients, ARV- associated hepatotoxicity.
Department of Molecular Biology, National AIDS Research Institute, Pune, Department of Molecular Biology, National AIDS Research Institute, Pune, Department of Molecular Biology, National AIDS Research Institute, Pune, Department of Molecular Biology, National AIDS Research Institute, Pune