HIV感染者DAT1 (VNTR)多态性的发生

Q4 Pharmacology, Toxicology and Pharmaceutics Current Pharmacogenomics and Personalized Medicine Pub Date : 2021-04-21 DOI:10.2174/1875692118666210421104202
HariOm Singh, S. Lata
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Reported literature indicates the correlation of DAT19/10 genotype with the risk of progression of human immunodeficiency virus (HIV) infection. \n\n\n\nTo assess the polymorphism in the human gene DAT1 including variable number tandem repeats (VNTR) from individuals having an infection of HIV. \n\n\n\nGenotyping was completed by performing a polymerase chain reaction (PCR) in a total of 165 HIV positive patients on ART treatment (34 were HIV-infected patients with hepatotoxicity, 131 HIV-infected patients) and 160 healthy controls without HIV infection. \n\n\n\nIncidence of DAT19/9, 8/9 genotypes, and allele with 9 repeats were higher in individuals having hepatotoxicity compared to those who do not have hepatotoxicity (5.9 vs. 0.8%, OR = 7.73; 2.9 vs. 0.8%, OR = 3.86; 20.58% vs. 14.12%, OR = 1.56). DAT19/10 genotype was related to severity of hepatotoxicity (OR = 1.86; P = 0.05). Upon comparison of genotype between individuals who do not have hepatotoxicity but having HIV infection and healthy controls without HIV infection, the dispersion of DAT1 10/11, 6/10 genotypes were greater in individuals with HIV infection (1.5% vs. 0.6%, OR = 2.73; 3.1% vs. 1.3%, OR = 2.73). DAT19/10 genotype was related to the people of advanced stage of HIV infection (OR = 2.05, P = 0.04). A higher incidence of DAT19/10 genotype was found in individuals with early stage of HIV infection than healthy controls (26.3 vs. 15.6%, OR = 1.93). In alcohol and tobacco consuming individuals with HIV infection and hepatotoxicity, DAT19/10 genotype has demonstrated hazard in the progression of HIV infection and increasing severity of hepatotoxic condition (OR = 1.40, P = 0.91, OR = 1.50; P = 0.91 and OR = 1.57, P = 0.39; OR = 2.70; P = 0.53). 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引用次数: 0

摘要

据报道,抗逆转录病毒治疗(ART)通过改变多巴胺活性转运蛋白(DAT)的表达而改变多巴胺能神经元的功能。含有依非韦伦药物的抗逆转录病毒治疗已显示出对中枢神经系统的不良反应。文献报道表明,DAT19/10基因型与人类免疫缺陷病毒(HIV)感染进展的风险相关。评估人类基因DAT1的多态性,包括来自HIV感染个体的可变数串联重复序列(VNTR)。通过聚合酶链反应(PCR)对接受抗逆转录病毒治疗的165例HIV阳性患者(34例为肝毒性HIV感染患者,131例为HIV感染患者)和160例未感染HIV的健康对照进行基因分型。DAT19/9、8/9基因型和9重复等位基因在肝毒性个体中的发生率高于无肝毒性个体(5.9 vs. 0.8%, OR = 7.73;2.9 vs. 0.8%, OR = 3.86;20.58% vs. 14.12%, OR = 1.56)。DAT19/10基因型与肝毒性严重程度相关(OR = 1.86;P = 0.05)。通过比较无肝毒性但感染HIV的个体与未感染HIV的健康对照者的基因型,感染HIV的个体中DAT1 10/11、6/10基因型的分散度更大(1.5%比0.6%,OR = 2.73;3.1% vs. 1.3%, OR = 2.73)。DAT19/10基因型与HIV感染晚期相关(OR = 2.05, P = 0.04)。早期HIV感染者中DAT19/10基因型的发生率高于健康对照组(26.3% vs. 15.6%, OR = 1.93)。在有艾滋病毒感染和肝毒性的酒精和烟草消费个体中,DAT19/10基因型在艾滋病毒感染的进展和肝毒性状况的严重程度增加中显示出危险(OR = 1.40, P = 0.91, OR = 1.50;P = 0.91, OR = 1.57, P = 0.39;Or = 2.70;P = 0.53)。在肝毒性患者中,使用DAT19/10基因型的奈韦拉平会增加肝毒性的严重程度(OR = 4.00, P = 0.41)。在艾滋病毒感染和肝毒性的个体中,酒精和奈韦拉平的使用以及DAT1 /10基因型显示出艾滋病毒感染进展和肝毒性严重程度增加的危险(OR = 1.47, P = 0.85;Or = 1.73;P = 0.32)。具有DAT19/10基因型的遗传多态性与HIV感染的进展和HIV相关疾病的进展有关。
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Occurrence of DAT1 (VNTR) Polymorphism in Individuals with HIV infection
Antiretroviral treatment (ART) have been reported to make changes in the functioning of dopaminergic neurons by altering the expression of dopamine active transporter (DAT). ART containing efavirenz drug have been related to show the adverse reactions on the central nervous system (CNS). Reported literature indicates the correlation of DAT19/10 genotype with the risk of progression of human immunodeficiency virus (HIV) infection. To assess the polymorphism in the human gene DAT1 including variable number tandem repeats (VNTR) from individuals having an infection of HIV. Genotyping was completed by performing a polymerase chain reaction (PCR) in a total of 165 HIV positive patients on ART treatment (34 were HIV-infected patients with hepatotoxicity, 131 HIV-infected patients) and 160 healthy controls without HIV infection. Incidence of DAT19/9, 8/9 genotypes, and allele with 9 repeats were higher in individuals having hepatotoxicity compared to those who do not have hepatotoxicity (5.9 vs. 0.8%, OR = 7.73; 2.9 vs. 0.8%, OR = 3.86; 20.58% vs. 14.12%, OR = 1.56). DAT19/10 genotype was related to severity of hepatotoxicity (OR = 1.86; P = 0.05). Upon comparison of genotype between individuals who do not have hepatotoxicity but having HIV infection and healthy controls without HIV infection, the dispersion of DAT1 10/11, 6/10 genotypes were greater in individuals with HIV infection (1.5% vs. 0.6%, OR = 2.73; 3.1% vs. 1.3%, OR = 2.73). DAT19/10 genotype was related to the people of advanced stage of HIV infection (OR = 2.05, P = 0.04). A higher incidence of DAT19/10 genotype was found in individuals with early stage of HIV infection than healthy controls (26.3 vs. 15.6%, OR = 1.93). In alcohol and tobacco consuming individuals with HIV infection and hepatotoxicity, DAT19/10 genotype has demonstrated hazard in the progression of HIV infection and increasing severity of hepatotoxic condition (OR = 1.40, P = 0.91, OR = 1.50; P = 0.91 and OR = 1.57, P = 0.39; OR = 2.70; P = 0.53). In patients with hepatotoxicity, nevirapine utilization with DAT19/10 genotype had demonstrated an increase in severity of hepatotoxicity (OR = 4.00, P = 0.41). In individuals with HIV infection and hepatotoxicity, alcohol and nevirapine usage along with DAT1 9/10 genotype have indicated a hazard for progression of HIV infection and increase in severity of hepatotoxicity (OR = 1.47, P = 0.85; OR = 1.73; P = 0.32). The genetic polymorphism with DAT19/10 genotype was linked with the progression of HIV infection and in the advancement of HIV-related illnesses.
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Current Pharmacogenomics and Personalized Medicine
Current Pharmacogenomics and Personalized Medicine Pharmacology, Toxicology and Pharmaceutics-Pharmacology
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期刊介绍: Current Pharmacogenomics and Personalized Medicine (Formerly ‘Current Pharmacogenomics’) Current Pharmacogenomics and Personalized Medicine (CPPM) is an international peer reviewed biomedical journal that publishes expert reviews, and state of the art analyses on all aspects of pharmacogenomics and personalized medicine under a single cover. The CPPM addresses the complex transdisciplinary challenges and promises emerging from the fusion of knowledge domains in therapeutics and diagnostics (i.e., theragnostics). The journal bears in mind the increasingly globalized nature of health research and services.
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