Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients.
Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients.
复制标题
DOI：
10.1002/mgg3.1764
复制
发表时间：
2021-10
影响因子：
2
通讯作者：
Guio H
中科院分区：
文献类型：
--
作者：
Levano KS;Jaramillo-Valverde L;Tarazona DD;Sanchez C;Capristano S;Vásquez-Loarte T;Solari L;Mendoza-Ticona A;Soto A;Rojas C;Zegarra-Chapoñan R;Guio H
我们确定了一个结核病患者队列中秘鲁人群中三种先前报道的抗结核药物代谢蛋白的遗传多态性频率：N-乙酰转移酶2（NAT 2），细胞色素P450 2 E1（CYP 2 E1）和芳基乙酰胺脱乙酰酶（AADAC）。我们对395名完成抗结核治疗的受试者进行了NAT 2的rs 1041983、rs 1801280、rs 1799929、rs 1799930、rs 1208和rs 1799931; CYP 2 E1的rs3813867和rs 2031920;以及AADAC的rs 1803155基因分型。74%的参与者是慢代谢基因型的携带者：NAT 2 *5，NAT 2 *6和NAT 2 *7，这些基因型增加了低剂量INH的敏感性，并增加了药物引起的肝损伤的风险。64%为野生型CYP 2 E1 *1A等位基因纯合子，这可能会增加肝毒性的风险。然而，16%的患者具有NAT 2快代谢者表型，这可能增加对INH获得耐药性的风险，从而增加多药耐药（MDR）或治疗失败的风险。秘鲁人rs 1803155（AADAC*2等位基因）的频率（99.9%）高于欧洲裔美国人、非洲裔美国人、日本人和韩国人。应进一步研究和考虑秘鲁人口中异烟肼代谢缓慢者的高流行率，以帮助个性化药物治疗方案，特别是在像秘鲁这样具有巨大遗传多样性的国家。这些数据将有助于秘鲁国家结核病控制计划制定新的治疗策略。应进一步研究和考虑秘鲁人口中异烟肼代谢缓慢者的高流行率，以帮助个性化药物治疗方案，特别是在像秘鲁这样具有巨大遗传多样性的国家。
We determined the frequency of genetic polymorphisms in three anti‐TB drug metabolic proteins previously reported: N‐acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1), and arylacetamide deacetylase (AADAC) within a Peruvian population in a cohort of TB patients. We genotyped SNPs rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931 for NAT2; rs3813867 and rs2031920 for CYP2E1; and rs1803155 for AADAC in 395 participants completed their antituberculosis treatment. Seventy‐four percent of the participants are carriers of slow metabolizer genotypes: NAT2*5, NAT2*6, and NAT2*7, which increase the sensitivity of INH at low doses and increase the risk of drug‐induced liver injuries. Sixty‐four percent are homozygous for the wild‐type CYP2E1*1A allele, which could increase the risk of hepatotoxicity. However, 16% had a NAT2 fast metabolizer phenotype which could increase the risk of acquiring resistance to INH, thereby increasing the risk of multidrug‐resistant (MDR) or treatment failure. The frequency of rs1803155 (AADAC*2 allele) was higher (99.9%) in Peruvians than in European American, African American, Japanese, and Korean populations. This high prevalence of slow metabolizers for isoniazid in the Peruvian population should be further studied and considered to help individualize drug regimens, especially in countries with a great genetic diversity like Peru. These data will help the Peruvian National Tuberculosis Control Program develop new strategies for therapies. High prevalence of slow metabolizers for isoniazid in the Peruvian population should be further studied and considered to help individualize drug regimens, especially in countries with a great genetic diversity like Peru.
登录
查看更多内容
影响因子：
6
作者：
Pontual, Yasmin;Pacheco, Vanessa S. S.;de Castro, Liane
通讯作者：
de Castro, Liane
影响因子：
2.9
作者：
Azuma, Junichi;Ohno, Masako;Kubota, Ryuji;Yokota, Soichiro;Nagai, Takayuki;Tsuyuguchi, Kazunari;Okuda, Yasuhisa;Takashima, Tetsuya;Kamimura, Sayaka;Fujio, Yasushi;Kawase, Ichiro
通讯作者：
Kawase, Ichiro
影响因子：
3.7
作者：
Ganachari, Malathesha;Ruiz-Morales, Jorge A.;Flores-Villanueva, Pedro O.
通讯作者：
Flores-Villanueva, Pedro O.
影响因子：
4.9
作者：
Sloan DJ;McCallum AD;Schipani A;Egan D;Mwandumba HC;Ward SA;Waterhouse D;Banda G;Allain TJ;Owen A;Khoo SH;Davies GR
通讯作者：
Davies GR
DOI：
10.1093/bioinformatics/btp121
发表时间：
2009-05-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Kuznetsov IB;McDuffie M;Moslehi R
通讯作者：
Moslehi R