title: Association of IL10, IL4, IFNG, and CTLA4 Gene Polymorphisms with Efavirenz Hypersensitivity Reaction in Patients Infected with Human Immunodeficiency Virus.
abstract: We evaluated interleukin-10 (IL10) －592 C/A, IL4－589 C/T, interferon gamma (IFNG)＋874 A/T, cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)＋49 A/G gene polymorphisms associated with efavirenz hypersensitivity reaction. A total of 63 human immunodeficiency virus-positive patients under treatment at a public hospital were included in the study, of whom 21 presented with efavirenz hypersensitivity. Patients who presented with efavirenz hypersensitivity reaction showed a higher frequency of the IL10 －592A allele than the controls (p＝0.028). The allele A was associated with increased risk of efavirenz hypersensitivity (odds ratio＝2.40). In case of IL4, a significant difference in the frequency of the IL4 －589 (C/T) polymorphism was not observed between patients and controls. A significant inverse correlation was observed when comparing the CTLA4＋49A/G and IL4 －589 C/T polymorphisms (r＝－0.650, p＝0.001); that is, the CTLA4 +49GG genotype, involved with the lowest capacity of inhibition, was inversely correlated IL4－589TT genotype, which induces high production of IL-4. With respect to the CTLA4＋49A/G and IFNG＋874T/A gene polymorphisms, significant differences in allele and genotype frequencies were not observed between the groups. Therefore, our data suggest that polymorphisms in regulatory regions of cytokine genes could modulate an individual's susceptibility to efavirenz hypersensitivity reaction.
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Ceará.
authors.forename: Raphael
authors.initials: R
authors.lastname: de Oliveira Rodrigues
authors.affiliation: Laboratory of Molecular Genetics, Department of Pathology and Forensic Medicine, Federal University of Ceará.
authors.forename: Silvia
authors.initials: S
authors.lastname: Helena Barem Rabenhorst
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Ceará.|Center for Health Sciences, University of Fortaleza.
authors.forename: Paulo
authors.initials: P
authors.lastname: Germano de Carvalho
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Ceará.
authors.forename: Greyce
authors.initials: G
authors.lastname: Luri Sasahara
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Ceará.
authors.forename: Luciana
authors.initials: L
authors.lastname: Mabel Ferreira Vasconcelos
authors.affiliation: Hospital São Jose de Doenças Infecciosas.
authors.forename: Érico
authors.initials: É
authors.lastname: Antônio Gomes de Arruda
authors.affiliation: Center for Health Sciences, University of Fortaleza.|Laboratory of Histocompatibility and Transplantation Immunology, Research Center for Hepatorenal Diseases, Federal University of Ceará.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fernandes Ribeiro da Silva
authors.affiliation: Laboratory of Histocompatibility and Transplantation Immunology, Research Center for Hepatorenal Diseases, Federal University of Ceará.
authors.forename: Ilana
authors.initials: I
authors.lastname: Farias Ribeiro
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Ceará.
authors.forename: Aparecida
authors.initials: A
authors.lastname: Tiemi Nagao-Dias
mesh_terms: D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects*; D060908:CTLA-4 Antigen / Q000235:genetics; D016022:Case-Control Studies; D003521:Cyclopropanes; D004342:Drug Hypersensitivity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics*; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D003521:Cyclopropanes; C573415:IFNG protein, human; C508609:IL10 protein, human; C508598:IL4 protein, human; D007155:Immunologic Factors; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; C098320:efavirenz
keywords: HIV/AIDS; efavirenz; hypersensitivity; pharmacogenetics and pharmacogenomics