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Genetic variants in CYP2A6 and UGT1A9 genes associated with urinary nicotine metabolites in young Mexican smokers.
The Pharmacogenomics Journal ( IF 2.9 ) Pub Date : 2020-01-21 , DOI: 10.1038/s41397-020-0147-4 Gissela Borrego-Soto 1 , Yadira X Perez-Paramo 2 , Gang Chen 2 , Sandra K Santuario-Facio 1 , Jesus Santos-Guzman 1 , Rodolfo Posadas-Valay 3 , Fatima M Alvarado-Monroy 1 , Isaias Balderas-Renteria 4 , Ramses Medina-Gonzalez 5 , Rocio Ortiz-Lopez 1 , Philip Lazarus 2 , Augusto Rojas-Martinez 1
The Pharmacogenomics Journal ( IF 2.9 ) Pub Date : 2020-01-21 , DOI: 10.1038/s41397-020-0147-4 Gissela Borrego-Soto 1 , Yadira X Perez-Paramo 2 , Gang Chen 2 , Sandra K Santuario-Facio 1 , Jesus Santos-Guzman 1 , Rodolfo Posadas-Valay 3 , Fatima M Alvarado-Monroy 1 , Isaias Balderas-Renteria 4 , Ramses Medina-Gonzalez 5 , Rocio Ortiz-Lopez 1 , Philip Lazarus 2 , Augusto Rojas-Martinez 1
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Nicotine is the major pharmacologically active substance in tobacco. Several studies have examined genotypes related to nicotine metabolism, but few studies have been performed in the Mexican population. The objective was to identify associations between gene variants in metabolizing enzymes and the urinary levels of nicotine metabolites among Mexican smokers. The levels of nicotine and its metabolites were determined in the urine of 88 young smokers from Mexico, and 167 variants in 24 genes associated with nicotine metabolism were genotyped by next-generation sequencing (NGS). Trans-3'-hydroxy-cotinine (3HC) and 4-hydroxy-4-(3-pyridyl)-butanoic acid were the most abundant metabolites (35 and 17%, respectively). CYP2A6*12 was associated with 3HC (p = 0.014). The rs145014075 was associated with creatinine-adjusted levels of nicotine (p = 0.035), while the rs12471326 (UGT1A9) was associated to cotinine-N-glucuronide (p = 0.030). CYP2A6 and UGT1A9 variants are associated to nicotine metabolism. 4HPBA metabolite was an abundant urinary metabolite in young Mexican smokers.
中文翻译：
CYP2A6 和 UGT1A9 基因的遗传变异与墨西哥年轻吸烟者尿中尼古丁代谢物相关。
尼古丁是烟草中主要的药理活性物质。几项研究检查了与尼古丁代谢相关的基因型，但在墨西哥人群中进行的研究很少。目的是确定墨西哥吸烟者代谢酶基因变异与尿液尼古丁代谢物水平之间的关联。对来自墨西哥的 88 名年轻吸烟者的尿液中尼古丁及其代谢物的水平进行了测定，并通过下一代测序 (NGS) 对与尼古丁代谢相关的 24 个基因的 167 个变异进行了基因分型。反式-3'-羟基-可替宁 (3HC) 和 4-羟基-4-(3-吡啶基)-丁酸是最丰富的代谢物（分别为 35% 和 17%）。 CYP2A6*12 与 3HC 相关（p = 0.014）。 rs145014075 与肌酐调整的尼古丁水平相关 (p = 0.035)，而 rs12471326 (UGT1A9) 与可替宁-N-葡萄糖苷酸相关 (p = 0.030)。 CYP2A6 和 UGT1A9 变体与尼古丁代谢相关。 4HPBA 代谢物在年轻的墨西哥吸烟者中是一种丰富的尿液代谢物。
更新日期：2020-01-21
中文翻译：
CYP2A6 和 UGT1A9 基因的遗传变异与墨西哥年轻吸烟者尿中尼古丁代谢物相关。
尼古丁是烟草中主要的药理活性物质。几项研究检查了与尼古丁代谢相关的基因型，但在墨西哥人群中进行的研究很少。目的是确定墨西哥吸烟者代谢酶基因变异与尿液尼古丁代谢物水平之间的关联。对来自墨西哥的 88 名年轻吸烟者的尿液中尼古丁及其代谢物的水平进行了测定，并通过下一代测序 (NGS) 对与尼古丁代谢相关的 24 个基因的 167 个变异进行了基因分型。反式-3'-羟基-可替宁 (3HC) 和 4-羟基-4-(3-吡啶基)-丁酸是最丰富的代谢物（分别为 35% 和 17%）。 CYP2A6*12 与 3HC 相关（p = 0.014）。 rs145014075 与肌酐调整的尼古丁水平相关 (p = 0.035)，而 rs12471326 (UGT1A9) 与可替宁-N-葡萄糖苷酸相关 (p = 0.030)。 CYP2A6 和 UGT1A9 变体与尼古丁代谢相关。 4HPBA 代谢物在年轻的墨西哥吸烟者中是一种丰富的尿液代谢物。
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