Association of genetic variations in HLA-B region with hypersensitivity to abacavir in some, but not all, populations

被引:192
作者
Hughes, AR
Mosteller, M
Bansal, AT
Davies, K
Haneline, SA
Lai, EH
Nangle, K
Scott, T
Spreen, WR
Warren, LL
Roses, AD
机构
[1] GlaxoSmithKline, Res Triangle Pk, NC 27709 USA
[2] GlaxoSmithKline, Harlow CM19 5AW, Essex, England
关键词
abacavir; HIV; HLA-B; hypersensitivity; linkage disequilibrium; pharmacogenetics; SNP;
D O I
10.1517/phgs.5.2.203.27481
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Abacavir is an effective antiretroviral drug used to treat HIV-1 infection. Approximately 5% of patients treated with abacavir develop a hypersensitivity reaction that requires discontinuation of the drug. In an initial pharmacogenetic study conducted in a predominantly White male population, multiple markers in the human leukocyte antigen (HLA)-B chromosomal region were associated with hypersensitivity to abacavir. The HLA-B*5701 association has now been confirmed in White males in a subsequent, larger study (n = 293, p = 4.7 x 10(-18)) and is also observed in White females (n = 56, p = 6.8 x 10(-6)) and Hispanics (n = 104, p = 2.1 X 10(-4)). HLA-B*5701 was not associated with hypersensitivity in Blacks (n = 78, p = 0.27). HLA-B*5701 alone lacks sufficient predictive value to identify patients at risk for hypersensitivity to abacavir across diverse patient populations. Efforts are ongoing to identify markers with sufficient sensitivity and specificity to be clinically useful. Even after a marker set is identified, appropriate clinical identification and management of hypersensitivity to abacavir must remain the cornerstone of clinical practice.
引用
收藏
页码:203 / 211
页数:9
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