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Prognostic significance of vascular endothelial growth factor polymorphisms in colorectal cancer patients

World Journal of Gastrointestinal Oncology 2017年第2期9卷 78-86页

作者： Gilmar Ferreira do Espírito Santo Bianca Borsatto Galera Elisabeth Carmen Duarte Elisabeth Suchi Chen Lenuce Azis Amilcar Sabino damazo Gabriela Tognini Saba Flávia de Sousa Gehrke ismael dale cotrim guerreiro da silva Jaques Waisberg Department of Surgery - Escola Paulista de Medicina Federal University of Sao Paulo Genetic Laboratory Basics Health Sciences Department Medical School of Federal University of Mato Grosso Tropical Medicine Division Medical School of Brasilia University Campus Darcy Ribeiro University Laboratory of Genetics of Morphology and Genetics Department Federal University of Sao Paulo Laboratory of Clinical Analysis ABC Medical School avenida Príncipe de Gales Laboratory of Molecular Gynecology Department of Gynecology Federal University of Sao Paulo rua Pedro de Toledo

AIM To investigate the associations of the genetic polymor-phisms of vascular endothelial growth factor A(VEGF-A)-1498C>T and-634G>C, with the survival of patients with colorectal cancer(CRC). METHODS A prospective cohort consisting of 131 Brazilians patients consecutively operated on with a curative intention as a result of sporadic colorectal carcinoma was studied. DNA was extracted from peripheral blood and its amplification and allelic discrimination for each genetic polymorphism was performed using the technique of polymerase chain reaction(PCR) in real-time. The real-time PCR technique was used to identify the VEGF-A-1498C>T(rs833031) and-634G>C(rs2010963) polymorphisms. Genotyping was validated for VEGF-A-1498C>T polymorphism in 129 patients and for VEGF-A-634G>C polymorphism in 118 patients. The analysis of association between categorical variables was performed using logistic regression, survival by Kaplan-Meier method and multivariate analysis by the Cox regression method. RESULTS In the univariate analysis there was a significant association(OR = 0.32; P = 0.048) between genotype CC of the VEGF-A-1498C>T polymorphism and the presence of CRC liver metastasis. There was no association between VEGF-A-1498C>T polymorphism and VEGF-A-634G>C polymorphism with further clinical or anatomopathologic variables. The genotype CC of the VEGF-A-1498C>T polymorphism was significantly correlated with the 5-year survival(P = 0.032), but not significant difference(P = 0.27) was obtained with the VEGF-A-634G>C polymorphism with the 5-year survival in the univariate analysis. The genotype CT(HR = 2.79) and CC(HR = 4.67) of the polymorphism VEGF-A-1498C>T and the genotype CC(HR = 3.76) of the polymorphism VEGF-A-634C>G acted as an independent prognostic factor for the risk of death in CRC patients. CONCLUSION The CT and CC genotypes of the VEGF-A-1498C>T and the CC genotype of the VEGF-A-634C>G polymorphisms are prognostic factors of survival in Brazilians patients with spora

关键词： Colorectal cancer Genetic polymorphisms Vascular endothelial growth factor-A Colorectal surgery Genetic variation

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Leptin Signaling Modulates Expression of Polycomb and Trithorax Complexes in the Brain of Fat Tissue Implanted Polycystic Ovarian Sindrome Mice

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American Journal of Molecular Biology 2014年第4期4卷 177-192页

作者： Eduardo Henrique da silva Freitas Samuel Marcos Ribeiro de Noronha Maria Nazareth Gamboa Ritto Carlos Fernandes Baptista ismael dale cotrim guerreiro da silva silvana Aparecida Alves Correa-Noronha Ivaldo da silva Gynecology Department Federal University of Sao Paulo Paulista School of Medicine (UNIFESP-EPM) Sao Paulo Brazil General Medicine Department Federal University of Rio de Janeiro State (UNIRIO) Rio de Janeiro Brazil Translacional Surgery Division Surgery Department Federal University of Sao Paulo Paulista School of Medicine (UNIFESP-EPM) Sao Paulo Brazil General and Specialized Surgery Department Federal University of Rio de Janeiro State (UNIRIO) Rio de Janeiro Brazil

The Polycystic Ovary Syndrome (PCOS) is the most common androgenic disorder in women during reproductive life. PCOS may also be accompanied by metabolic syndrome and recent studies point to leptin as playing a role in disrupting infertility and in changing the energy balance in obese mice through its action on the hypothalamus. The aim is to assess the expression of the Polycomb & Trithorax Complexes genes in brain of mice transplanted with fat tissue from normal mice, in order to better understand the neuronal mechanisms underlying the reversion of PCOS. Three B6 V-Lepob/J mouse groups: Normal weight, obese and seven-day-treatment obese had their brain RNA extracted and submitted to an 84 Polycomb & Trithorax Complexes genes PCR Array plate and MetacoreTM pathways localization. Genomic profiles obtained were compared to the ones of the normal-weight-mice group. Differentially expressed genes were 13% and 26% respectively to control and treatment. Major changes were in genes: Snai1/31;Smarca1/?17;Dnmt3b/4.7;Ezh1/ 15. Altered genes were associated to canonical pathways and provided 3 networks related to epigenetics. Underlying neuronal changes caused by leptin in obese mice brain, there is an important role being played by the histone code. Here there is evidence that leptin drives the chromatin packing to a more condensed pattern. Upregulation of methyltransferase genes, like Ezh1, favors this thought. In summary the Polycomb & Trithorax complexes might answer for the silencing of some downregulated genes in the obese mice brain when exposed to leptin.

关键词： Polycistic Ovarian Sindrome Obesity Polycomb and Trithorax Complexes Leptin Fat Mouse

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Angiotensin-(1-7)Changes Apoptosis-Related Genes Expression in Human Breast Cancer Cell Line T47D

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Journal of Cancer Therapy 2014年第14期5卷 1412-1422页

作者： Cheryl Alecrim Santos Gabriela Soares da silva Brito silvana Aparecida Alves Correa de Noronha Samuel Marcos Ribeiro de Noronha Suma Imura Shimuta Clovis Ryiuchi Nakaie ismael dale cotrim guerreiro da silva Department of Gynecology Federal University of Sao PauloSao PauloBrazil Department of Surgery Federal University of Sao PauloSao PauloBrazil Department of Biophysics Federal University of Sao PauloSao PauloBrazil

Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide of the renin-angiotensin system with vasodilator and anti-proliferative properties. In the present study, we aim to investigate whether Ang-(1-7) induces apoptosis in breast cancer cells and whether the altered expression of apoptosis-related genes is involved in this process. Human breast cell line T47D was treated with angiotensin-(1-7) and angiotensin II (Ang II). Cell proliferation and apoptosis were quantified using hemocytometer and flow cytometry, respectively. The expression of 84 apoptosis-related genes was evaluated through qPCR array. Ang-(1-7), as opposed to Ang II, decreased proliferation and increased apoptosis in T47D cells. Moreover, many pro-apoptotic genes were up-regulated, such as BAK1, BAX, BCL2L1, BID and BIK. In addition, some anti-apoptotic genes as AKT1 and XIAP were down-regulated by heptapeptide. Although a deeper study should be performed, our results support the hypothesis that Ang-(1-7) could change the expression of several genes related to apoptosis, interfering directly in the molecular pathways associated with the survival of breast cancer cells.

关键词： Angiotensin-(1-7) Breast Cancer Cells Apoptosis qPCR Array

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Increased Risk of Acute Myeloid Leukemia in Patients with CYP1A1 Polymorphisms

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Journal of Cancer Therapy 2013年第5期4卷 971-977页

作者： Luís Arthur Flores Pelloso ismael dale cotrim guerreiro da silva Naiara Correa Nogueira de Souza Mihoko Yamamoto Maria de Lourdes L.Ferrari Chauffaille Section of Hematology and Blood Transfusion Department of Clinical and Experimental OncologyFederal University of Sao Paulo(UNIFESP-EPM)Sao PauloBrazil Pharmacovigilance Pharmaceutical Product DevelopmentInc.Sao PauloBrazil Disciplina de Ginecologia UNIFESP-EPM Federal University of Sao Paulo(UNIFESP-EPM)Sao PauloBrazil

Acute Myeloid Leukemia (AML) is a group of genetically diverse hematopoietic malignancies arising from cell progenitors developing in the myeloid pathway or from primitive stem cells. Genetic susceptibility of AML may account for an increased risk of AML due to partial metabolism of or biocativation of carcinogens. Chemical compounds are metabolized by a two-tiered phase detoxifying system. Polymorphisms in these pathways may lead to DNA damage and development of AML. We determined the frequencies of carcinogen metabolism gene polymorphisms (CYP1A1, del{GSTM1} and del{GSTT1}) in a case control-study based on polymorphism analysis. Fifty-eight consecutively AML patients (median age 62 years) and 174 sex and age-matched control group were assessed by a PCR-RFLP assay. There were 51 de novo and 7 secondary AML. CYP1A1*2A and CYP1A1*2C polymorphisms were more frequent in CG than AML p 0.001 and in contrast, CYP1A1*3 and CYP1A1*4 were more frequent in AML than CG p 0.001. There were no differences in del{GSTM1} neither del{GSTT1} between AML and CG (p = 0.999 and p = 0.539). Odds ratio for AML in patients harboring CYP1A1*3 was 2.36 (95% CI 1.2 - 4.5), 2.38 for CYP1A1*4 (95% CI 0.8 - 6.8). Adjusted OR was 2.63 for CYP1A1*3 (95% CI 1.4 - 5.1) and 2.66 for CYP1A1*4 (95% CI 0.9 - 7.8). In the multivariate analysis CYP1A1*3 polymorphism was a risk factor for AML with an OR for 3.99 (95%CI 1.9 - 8.6). To the best of our knowledge this is the first study to show that CYP1A1*3 heterozygous genotypes increase the risk of AML. Our data support that inherited absence of this carcinogen detoxification pathway may be an important determinant of AML.

关键词： Acute Myeloid Leukemia Karyotype GSTM1 GSTT1 CYP1A1 Gene Polymorphisms Genetic PolymorPhisms Biomarker

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Viscum Album Modulates Apoptotic Related Genes in Melanoma Tumor of Mice

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American Journal of Molecular Biology 2014年第2期4卷 49-58页

作者： Anamaria da silva Facina Gil Facina ismael dale cotrim guerreiro da silva Giovana Aparecida Goncalves Fernando Augusto de Almeida silvana Aparecida Alves Correa de Noronha Samuel Marcos Ribeiro de Noronha Mary Uchiyama Nakamura Departament of Dermatology Federal University of Sao PauloSao PauloBrazil Department of Gynecology Federal University of Sao PauloSao PauloBrazil Department of Surgery Federal University of Sao PauloSao PauloBrazil Departament of Obstetrics Federal University of Sao PauloSao PauloBrazil

Cancer is a major public health problem throughout the world. It is estimated that one third of the American population will develop the disease at some time during their lifetimes. Among these, melanoma will account for 7% of the cases. In Brazil, in 2012, it is estimated that over six thousand new melanoma cases occurred. During recent years, the incidence of melanoma has increased, mainly due to a more constant exposure of the skin to sunlight. In this work, our aim is to assess the expression of apoptotis-related genes melanoma tumors in mice treated with Viscum album (VA). This will allow us to better understand the molecular mechanisms underlying tumor cell death activation caused by this compound. Our results clearly demonstrate upregulation of pro apoptotic genes (Trp53bp2, Nol3, Fadd, Tnfsf10, Traf1, Traf2, Cflar, Card10, Nod1, Casp 2, Casp7, Xiap, dad1, and Dffb). Further bioinformatics-based tool analysis allowed us to assess which specific cell death-related intracellular pathways were activated by VA treatment. Two major effects of VA in melanoma cells could be observed: generation of an immunomudulatory Th-1 like action, recruiting several interleukines, and cell death activation through Caspase7, associated uspstream with Card10 and downstream with CAD. In summary, VA modulates apoptosis related genes in cancer melanoma cells. Although a deeper study should be conducted, VA seems to interfere with important signaling pathways within melanoma cells that control the cellular mechanisms of apoptosis activation. Therapeutic approaches using VA as an antineoplastic and adjuvant medication compounding should be considered.

关键词： Viscum Album Melanoma Apoptosis Pathways PCR Array Immunohistochemistry

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Initial Analysis of Lipid Metabolomic Profile Reveals Differential Expression Features in Myeloid Malignancies

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Journal of Cancer Therapy 2015年第15期6卷 1262-1272页

作者： Adriana Ramos de Oliveira ismael dale cotrim guerreiro da silva Edson G. Lo Turco Helio Alves Martins Júnior Maria de Lourdes L. Ferrari Chauffaille Chauffaille Department of Clinical and Experimental Oncology Federal University of Sao Paulo Sao Paulo Brazil Gynecologic Department Federal University of Sao Paulo Sao Paulo Brazil

The purpose of this preliminary study was to determine the comparative lipid profile of blood plasma samples of healthy individuals and patients with Myeloproliferative Neoplasms. Methods: Untargeted Shotgun MS/MS Analysis was performed to evaluate plasma samples from 153 participants, being 90 of the Control Group, 43 Myeloproliferative Neoplasms (MPN), 11 Myelodysplastic Syndromes (MDS) and 9 Acute Myeloid Leukemias (AML). Lipids were extracted from plasma using the Bligh-Dyer protocol. data were acquired using the AB-Sciex Analyst TF, processed using the AB-Sciex LipidViewTM and the web-based analytical pipeline MetaboAnalyst 2.0 (***). Results: Untargeted analysis identified in negative and positive-modes a total of 658 features at 2 ppm resolution. PCA and PLS-da analysis revealed clear discrimination among groups, in particular for AML patients. Main lipid groups differentially expressed were: Monoacylglycerols (MAG), Glucosylceramide E (GlcdE), Ethyl Esters (EE), Lysophosphatidic acid (LPA), Sulfoquinovosil diacylglycerols (SQDG), Monoglycerols (MG), Methyl Ethanolamines (ME), Lysophosphatidylcholines (LPC), Dimethyl Phosfatidyletanolamines (DMPE), Monometylphosphatidiletanolamines (MMPE), Ceramide-1-phosphate (CerP), Glicerophosphoglycerols (GP), Lysomonomethyl-Phosphatidylethanolamines (LMMPE), Phosphatidic Acids (PA), Ergosterols (ERG), Glycerophosphoserine (PS), Diacylglycerols (daG), Hexocylceramides (HexCer) and Lanosterol (Lan). ROC Curve Analysis revealed Total LMMPE as the strongest discriminating marker between Controls from Patients. In addition, these lipids were also able to differentiate MDS and AML from NPM. Conclusions: The Myeloproliferative Neoplasms from the point of view of global plasma lipidomics are accompanied by several modifications. In particular, the Lysomonomethyl-Phosphatidylethanolamines (LMMPE) seems to play important differentiating roles among them.

关键词： Lipids Lipidomics Myeloproliferative Neoplasms Mass Spectrometry

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Gene Expression Analysis of Extracellular Matrix and Cytokines after Uterine Artery Embolization

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Open Journal of Obstetrics and Gynecology 2014年第15期4卷 935-943页

作者： André Bernardo Tatiana Carvalho de Souza Bonetti ismael dale cotrim guerreiro da silva Mariano Tamura Vieira Gomes Rodrigo Aquino Castro Manoel Joao Batista Castello Girao Claudio Emilio Bonduki Gynecology Department Paulista School of MedicineFederal University of Sao Paulo(EPM-UNIFESP)Sao PauloBrazil

Arterial embolization of myomas (AEM) is an established option for the conservative treatment of uterine leio-myomas;it treats all present uterine nodules at once, is less invasive than other procedures and effective in controlling symptoms, and does not require long term hospitalizations. Nevertheless, the potential impact on endometrial morphological and functional outcomes after the procedure is still controversial based on reports of endometritis or eventual transient ischemia. This study evaluated endometrial reorganization in uterine leiomyoma patients, before and after AEM, through gene expression analyses of extracellular matrix and cytokines genes in theendometrial tissue. Eight patients with leiomyomas were evaluated before AEM and 6 months after. The examinations included transvaginal pelvic ultrasonography, dosing of the follicle-stimulating hormone, and endometrial biopsy during the second phase of the menstrual cycle. RNA was extracted from endometrial samples, cDNA was synthesized, and applied on PCR arrayTM plates to evaluate the expression of extracellular matrix (ECM) genes and cytokines and their receptors’ genes (CYT). The ECM overexpressed genes were MMP (1, 3, 10, 11, and 14), CTGF1, ICAM1, TBHS1, ITGA2, ITGA3, ITGB3, COL7A1, COL12A, SPP1, and TNC;AdaMTS8 was underexpressed. The CYT overexpressed genes were SPP1, BCL6, CXCL12, IL-8, and CEBPB;CXCL13 and CCL21 were underexpressed. The ECM results showed overexpression of proteases that are responsible for dysfunctions in the ECM, and of genes responsible for adhesion and membrane components. The CYT results showed overexpression of chemokines responsible for endometrial repair, and underexpression of cytokines involved in inflammatory processes in the endometrial tissue. AEM treatment did not negatively affect the endometrial function at 6 months after embolization. This study broadens the knowledge about using a procedure that is relevant to the treatment of leiomyomas and contributes to the es

关键词： Component Myoma Arterial Embolization of Myomas Extracellular Matrix Cytokines

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Effects on Cell Viability and on Apoptosis in Tumoral(MCF-7)and in Normal(MCF10A)Epithelial Breast Cells after Human Chorionic Gonadotropin and Derivated-Angiotensin Peptides Treatments

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Journal of Cancer Therapy 2013年第7期4卷 65-69页

作者： silvana Aparecida Alves Correa de Noronha Werica Bernardo Alexandre Jesus Barros Clovis Ryuichi Nakaie Suma Imura Shimuta ismael dale cotrim guerreiro da silva Samuel Marcos Ribeiro de Noronha Laboratorio de Cirurgia Translacional Departamento de CirurgiaUniversidade Federal De Sao Paulo/Escola Paulista De MedicinaSao PauloBrazil Laboratorio de Ginecologia Molecular Universidade Federal de Sao PauloSao PauloBrazil Departamento de Biofísica Universidade Federal de Sao PauloSao PauloBrazil

Angiotensin-(1 - 7) [Ang-(1 - 7)] is an endogenous heptapeptide hormone of the renin-angiotensin system that has antiproliferative properties. The aim of this work was to evaluate the anti-proliferative and pro-apoptotic properties of Ang-(1 - 7) and of Ang-(1 - 7)-substituents 9-fluorenylmethyloxycarbonyl (Fmoc) e Ang II-derivatives containing the TOAC (2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid) in normal (MCF10A) and in tumoral (MCF7) epithelial mammary cell lines. Both cell lines received an hCG and angiotensin peptides 24-hour treatment, in combination or alone followed by cell viability, apoptosis and cell cycle assays performed by flow cytometer (GUAVA). After hCG, Ang-(1 - 7), hCG + Ang-(1 - 7) and hCG + Ang-(1 - 7)-Fmoc treatments, MCF7 displayed cell viability decrease and mid-apoptosis increase. We also observed cell viability decrease in MCF10A after Ang-(1 - 7), Ang-(1 - 7) Fmoc and hCG + AngII Toac treatments. These cells had an increase in late apoptosis and necrosis after AngII Toac, hCG + Ang-(1 - 7) and hCG + Ang-(1 - 7)-Fmoc treatments. Regarding the cell cycle analysis, we did not observed any changes in cell cycle phases. In summary, cell viability was decreased and apoptosis (initial, mid and late) was increased after hCG and/or Ang-(1 - 7) peptides treatments. These results point out hCG and Ang-(1 - 7) as effective compounds to inhibit cell proliferation, since they decrease cell viability and increase apoptosis in both normal and in tumoral breast cells, being the effect more pronounced in the tumoral cell line. Our results support the idea of investigating more closely the putative use of these compounds as novel therapeutic agents for breast cancer.

关键词： Angiotensin II Angiotensin 1-7 Angiotensin II Type 1 Receptor(AT1R) Breast Cancer Apoptosis Human Chorionic Gonadotropin

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Plasma Levels of Angiotensin-Converting Enzymes 1 and 2 and <i>AGTR</i>2 (T1247G and A5235G) Gene Polymorphisms Are Associated to Breast Cancer Progression

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Journal of Cancer Therapy 2013年第9期4卷 1403-1410页

作者： Maria Del Carmen Garcia Molina Wolgien ismael dale cotrim guerreiro da silva Afonso Celso Pinto Nazário Clovis Riyuchi Nakaie silvana Aparecida Alves Corrêa de Noronha Samuel Marcos Ribeiro de Noronha Gil Facina Biophisics Department Escola Paulista de Medicina da Universidade Federal de Sao Paulo (EPM-UNIFESP) Sao Paulo Brazil Gynecology Department Escola Paulista de Medicina/Universidade Federal de Sao Paulo (EPM-UNIFESP) Sao Paulo Brazil Surgery Department Escola Paulista de Medicina/Universidade Federal de Sao Paulo (EPM-UNIFESP) Sao Paulo Brazil

Background: Breast cancer is the most common type of cancer among women. Diagnosed and treated timely, patients may have good prognostics. In Brazil, in 2012, the estimate of new cases was 52,680 and the number of registered deaths in 2012 was 12,852. The Renin-Angiotensin System (RAS) is known for its role in arterial hypertension and in other cardiovascular diseases. Angiotensin-Converting Enzyme 2 (ACE2) is the key to Ang-(1-7) formation, and counterbalances the ACE1/AngII/AGTR1 axis actions. RAS components have complex interactions with different tissues and their actions are not restricted to the cardiovascular system. Recently, the RAS has been associated with different types of cancers and in particular with gynecological cancers. Objectives: Our aim is to investigate possible associations between allelic distribution of two genetic polymorphisms in the AGTR2 receptor with ACEs 1 and 2 plasma levels among women with breast cancer. Patients and Methods: Patients with breast cancer were genotyped for two polymorphisms of the AGTR2 (T1247G and A5235G). Genotyping assays (TaqMan) were performed with genomic DNA extracted from blood cells. ACEs plasma level measurements were conducted in women from the breast-cancer group (N = 53). ACEs were measured in the plasma of these patients using ELISA kits. Results: SNPs genotype distribution is correlated with ACEs plasma levels. ACEs plasma levels are also correlated with clinical variables and ACE2 high levels are associated with better prognostics. Conclusions: Changes in circulating levels of ECA1/AngII ECA2/ Ang-(1-7) determine the magnitude of the inflammatory response that an individual can trigger and the variation in ACE 1 and 2 plasma level measurements in the blood of breast cancer patients suggests an association with the process of mammary carcinogenesis. Thus, the RAS may be associated with the process of mammary carcinogenesis by both genotypic variations of RAS components and by circulating levels of ACEs

关键词： Angiotensin-Converting Enzyme 1 Angiotensin-Converting Enzyme 2 Angiotensin II Type 2 Receptor Breast Neoplasm ACEs Plasma Level Genetic Polymorphisms

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Prevalence of Human Leukocyte Antigen HLA-B*5701 in HIV-1 Infected Individuals in Brazil

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Open Journal of Genetics 2014年第1期4卷 56-62页

作者： Claudinéia de Araújo Cristina Valetta de Carvalho Miriam Estela de Souza Freire Amanda Yamaguti Ivens Cuiabano Scaff Fernando José de Souza Flávia Galindo Silvestre silva Ricardo Sobhie Diaz ismael dale cotrim guerreiro da silva Department of Gynecology Molecular Gynecology Laboratory Federal University of S&atildeo Paulo S&atildeo Paulo Brazil State Department of Health of Mato Grosso Cuiabá Brazil Unirondon University Cuiabá Brazil Infectious Diseases Division Federal University of Mato Grosso Cuiabá Brazil Imunogenetics Laboratory General University Hospital Cuiabá Brazil

This study was designed to establish the prevalence of HLA-B*5701 at HIV-1 infected individuals in Brazil. A total of 517 consecutive individuals were followed in this study from February 2009 through July 2011. The presence of HLA-B*5701 was determined by Nested-PCR with HLA-B*57 and HLA-B*5701 sequence-specific primers (PCR-SSP). The expression of HLA-B*57 was negative in the 385 (74.5%) and positive in the 103 (19.9%) of infected individuals. Among these, the expression of HLA-B5701 was positive in the 29 (5.6%) of individuals. No demographic or ethnic differences were found between HLA-B*57/HLA-B*5701 HIV-1 negative patients, with a prevalence of Caucasians (57.1%) individuals. During the period of study, 68 patients were submited to an abacavir contain- ing regimen. The HLA-B*5701 allele was observed in 7 (10.3%) patients, with a significant incidence of Hypersensitivity reactions at 4 of them (p < 0.001). Conclusions: Although Brazilian population consists of a mixture of individuals of Caucasian, African and Native American genetic background, prevalence of HLA-B*5701 in this population is similar to the one found in pure Caucasians.

关键词： Immunogenetics Human Immunodeficiency Virus HLA-B*5701 Antigen Human Abacavir

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