Singh Hari Om, Jadhav Sushma, Samani Dharmesh, Dhole Tapan N
1Department of Molecular Biology, National AIDS Research Institute, Pune, India; 2Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, 226014-Lucknow, India.
Curr Genomics. 2019 Feb;20(2):134-150. doi: 10.2174/1389202920666190325161439.
Micro RNAs act as a regulatory layer for pharmacogenomics-related gene ex-pression. It could play a role in the efficacy and toxicity of the drug. The SNPs in miRNA genes are linked with different functional consequences.
Hence, we examined the miR (146a G/C, 149C/T, and 196aC/T) polymorphisms in 34 pa-tients with hepatotoxicity, 123 patients without hepatotoxicity, and 155 healthy controls using a PCR-RFLP method.
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).
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.
微小RNA作为药物基因组学相关基因表达的调控层，可能在药物的疗效和毒性方面发挥作用。微小RNA基因中的单核苷酸多态性与不同的功能后果相关。
因此，我们采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，检测了34例肝毒性患者、123例无肝毒性患者和155例健康对照者的miR（146a G/C、149C/T和196aC/T）多态性。
在肝毒性患者中，miR196a CT基因型和联合基因型GCT显示出肝毒性严重程度的风险，具有临界显著性（OR=2.08，P=0.07；OR=2.88，P=0.06）。在比较肝毒性患者和健康对照者时，联合基因型CCC和GCT显示出对肝毒性严重程度的易感性（OR=2.89，P=0.05；OR=2.60，P=0.09）。miR196 TT基因型与晚期HIV疾病阶段的个体相关（OR=3.68，P=0.04）。在饮酒且无肝毒性的HIV患者中，miR 196a CT基因型显示出获得肝毒性的易感性，具有临界显著性（OR=2.36，P=0.06）。
miR149 TT和196a TT基因型在无肝毒性的HIV患者中显示出使用奈韦拉平获得肝毒性的风险（OR=4.19，P=0.07；OR=1.97，P=0.84）。在有和无肝毒性的HIV患者中，miR 196a CT基因型分别显示出联合使用酒精和奈韦拉平获得肝毒性及其严重程度的风险（OR=14.18，P=0.08；OR=2.29，P=0.08）。在多因素逻辑回归中，服用奈韦拉平的情况下，196a CT基因型是肝毒性严重程度的独立危险因素（OR=5.98，P=0.005；OR=2.38，P=0.05）。结论：总之，miR196a C/T多态性以及联合基因型GCT和CCC可能会增加获得肝毒性及其严重程度的风险。
