In:
Pharmacogenomics, Future Medicine Ltd, Vol. 10, No. 4 ( 2009-04), p. 531-540
Abstract:
Aims: Sulfamethoxazole in combination with trimethoprim (cotrimoxazole) is used for prophylaxis and treatment of several opportunistic infections in HIV-infected patients. It is associated with a high incidence of hypersensitivity reactions, which is thought to have an immune basis. Genetic polymorphisms in MHC are known to predispose to hypersensitivity reactions to a structurally diverse group of drugs in HIV-positive patients. The aim of the study was to determine whether functional polymorphisms in TNF, LTA, HSPA1L and HLA-DRB1 genes influence the risk of cotrimoxazole hypersensitivity in HIV-infected patients. Methods: We genotyped 136 HIV-positive patients with (n = 53) and without (n = 83) cotrimoxazole hypersensitivity using a combination of PCR-based techniques, including PCR-restriction fragment length polymorphisms, PCR-sequence specific oligonucleotides and real-time PCR. Genotypes and the haplotype frequencies were analyzed using the χ 2 test in the Haploview and CLUMP programs. Results: No statistically significant difference in SNP or haplotype frequencies were found in HIV-infected sulfamethoxazole hypersensitive patients compared with controls. Conclusion: Our data show that MHC polymorphisms are not major predisposing factors for cotrimoxazole hypersensitivity, although we cannot exclude a minor contribution. An environmental factor (i.e., HIV infection) seems to predominate over any of the genetic factors so far investigated in increasing the risk of cotrimoxazole hypersensitivity.
Type of Medium:
Online Resource
ISSN:
1462-2416
,
1744-8042
Language:
English
Publisher:
Future Medicine Ltd
Publication Date:
2009
SSG:
15,3
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