Interleukin-10 gene polymorphism (−1082G/A) and allergy to efavirenz in patients infected with human immunodeficiency virus

Rodrigues, Rodrigo Rodrigues; Carvalho, Paulo Germano de; Arruda, Érico Antônio Gomes de; Rabenhorst, Sílvia Helena Barem; Silva, Sílvia Fernandes Ribeiro da; Ribeiro, Ilana Farias; Lima, Denise Girão Limaverde; Nagão-Dias, Aparecida Tiemi

doi:10.1016/j.bjid.2014.01.009

Cited by 12 publications

(9 citation statements)

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“…We have observed in a previous report that the -1082 AA genotype was much more frequent in HIV-positive patients allergic to efavirenz than in nonallergic patients (P = .019; OR = 3.625; 95%CI = 1.210 to 10.860). 31 Comparing our present work with previous reports, one can hypothesize that low production of IL-10 is a risk factor for drug allergy but a protection against nonallergic hypersensitivity.…”

Section: Discussionsupporting

confidence: 81%

Polymorphism of IL10, IL4, CTLA4, and DAO Genes in Cross‐Reactive Nonsteroidal Anti‐inflammatory Drug Hypersensitivity

Vasconcelos

Rodrigues

Albuquerque

et al. 2017

The Journal of Clinical Pharma

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Our aim was to evaluate genetic polymorphism of molecules involved in immunoregulatory/allergic processes in patients who presented with cutaneous hypersensitivity caused by chemically unrelated nonsteroidal anti-inflammatory drugs. Polymorphisms at IL10 (-1082 G>A), IL4 (-589 C>T), CTLA4 (+49A>G), and DAO (+8956 C>G) genes were studied in 55 cases and 97 controls by the polymerase chain reaction-restriction fragment length polymorphism technique. With regard to the polymorphism at IL10 -1082, higher frequencies of the AG genotype (57% vs 39%) and G allele carriers (70% vs 48%) were found among the patients, indicating a risk effect (odds ratio [OR] = 2.56 and P = .01 for AG genotype and OR = 2.52; P = .01 for AG/GG). For the CTLA4 +49 A/G single-nucleotide polymorphism (SNP), AG genotype (31.0%) (P = .02) and G carrier (54.0%) (P = .05) frequencies were found to be significantly lower in the patient group compared with the control group (51.0% and 69.0%, respectively). The SNP DAO +8956 C>G was associated with a strong protective effect, with OR values of 0.83 for CG and 0.11 for GG genotype (P = .04 for the codominant model), suggesting an allele dose effect. The combination of IL10 and DAO SNPs in a multivariate model did not alter the OR values, suggesting independent effects for both SNPs. The results are striking. In conclusion, these results suggest that polymorphisms in regulatory targets of the immune response and in DAO gene could modulate an individual's susceptibility to nonsteroidal anti-inflammatory drug hypersensitivity reactions. Further studies will be necessary to complement our results.

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Section: Discussionsupporting

confidence: 81%

Polymorphism of IL10, IL4, CTLA4, and DAO Genes in Cross‐Reactive Nonsteroidal Anti‐inflammatory Drug Hypersensitivity

Vasconcelos

Rodrigues

Albuquerque

et al. 2017

The Journal of Clinical Pharma

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“…In our previous study (12), we found a significant association between IL10 polymorphism ( 1082 G ＞ A) and efavirenz hypersensitivity reaction. Thus, our goal here was to evaluate polymorphisms in IL10 592 C A, IL4 589 C T, IFNG 874 A T, and CTLA4 49 A G genes in the same HIV-positive patients with efavirenz hypersensitivity reaction and in control patients, as evaluated before (12).…”

Section: Introductionmentioning

confidence: 70%

“…Our group has previously investigated IL10 ( 1082 G A) gene polymorphism in efavirenz hypersensitivity reaction (12). The frequencies of the 1082AA genotype and of the 1082A allele were higher in the case group than in controls (12).…”

Section: Discussionmentioning

confidence: 99%

“…Single nucleotide polymorphisms (SNPs) in cytokine and immunoregulatory molecule genes may contribute to the evaluation of individual susceptibility to several diseases including drug allergies (10,11). In our previous study (12), we found a significant association between IL10 polymorphism ( 1082 G ＞ A) and efavirenz hypersensitivity reaction. Thus, our goal here was to evaluate polymorphisms in IL10 592 C A, IL4 589 C T, IFNG 874 A T, and CTLA4 49 A G genes in the same HIV-positive patients with efavirenz hypersensitivity reaction and in control patients, as evaluated before (12).…”

Section: Introductionmentioning

confidence: 93%

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Association of <i>IL10, IL4, IFNG</i>, and <i>CTLA4</i> Gene Polymorphisms with Efavirenz Hypersensitivity Reaction in Patients Infected with Human Immunodeficiency Virus

et al. 2017

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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.

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“…During HIV infection, AA was detected in 62% of allergic patients, while GG and GAin 69% of patients without allergies. Moreover, it was found that the polymorphism of interleukin -10 in position -1082 (A/G) is directly related to the development of allergic reactions to efavirenz [62].…”

Section: Immune Reactionmentioning

confidence: 99%

A Modern View of the Pathogenesis of Allergy with Drug Etiology

Mavlyanov

Ashirmetov

Mavlyanov

et al. 2016

Journal of Life Sciences Research

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Nowadays many diseases are associated with a high risk of drug allergy, and this risk can vary greatly depending on the type of disease. With the progression of disease in HIV-infected patients is increased IgE and decreased the number of CD4+ T-cells. In this case violated the ratio of interferon-gamma-producing (Th1 type) clones of CD4+ T-cells and IL-4-producing (Th2 type) clones of CD4+ T-cells. In HIV-infected patients, there is the high risk of developing allergies in the form of skin rashes and temperature, and severe skin syndromes Stevens-Jones (SJS) and toxic epidermal necrolysis (TEN) in 6%-10% of cases. CD4+ T cells secrete cytokines, for instance Interleukin (IL-5), Gransim and Eotaxin involve eosinophils to be grown and differentiated. Studies on the antigenicity of antibiotics demonstrated the potential relevance of both categories of drug allergy: hapten and p-i models. In patients with allergic reaction to piperacillin, this medication acts as the hapten, with the formation of the immunogenic conjugate piperacillin-albumin, which stimulates the drug-responsive T-cells. Immunogenetic factors have been identified as risk indicators for the development of hypersensitivity reactions to the representatives of many classes of drugs, such as Abacavir and Nevirapine, Carbamazepine and Allopurinol, etc. Thus, considering the huge genetic polymorphism in systems of drug metabolism in the body and in the systems contributing immune response to the resulting products of conjugation of hapten-protein, evident is the need to further study the role of these systems in the occurrence of adverse reactions to drug therapy, in particular, in the development of allergic complications.

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Interleukin-10 gene polymorphism (−1082G/A) and allergy to efavirenz in patients infected with human immunodeficiency virus

Cited by 12 publications

References 20 publications

Polymorphism of IL10, IL4, CTLA4, and DAO Genes in Cross‐Reactive Nonsteroidal Anti‐inflammatory Drug Hypersensitivity

Polymorphism of IL10, IL4, CTLA4, and DAO Genes in Cross‐Reactive Nonsteroidal Anti‐inflammatory Drug Hypersensitivity

Association of <i>IL10, IL4, IFNG</i>, and <i>CTLA4</i> Gene Polymorphisms with Efavirenz Hypersensitivity Reaction in Patients Infected with Human Immunodeficiency Virus

A Modern View of the Pathogenesis of Allergy with Drug Etiology

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