Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384.

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Serval ID
serval:BIB_8AFEA9B3C46F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384.
Journal
Journal of Neurovirology
Author(s)
Leger P.D., Johnson D.H., Robbins G.K., Shafer R.W., Clifford D.B., Li J., McLaren P.J., Haas D.W.
ISSN
1538-2443 (Electronic)
ISSN-L
1355-0284
Publication state
Published
Issued date
2014
Volume
20
Number
3
Pages
304-308
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish PDF : Short Communication
Abstract
Stavudine (d4T) was, until recently, one of the most widely prescribed antiretroviral drugs worldwide. While there has been a major shift away from d4T use in resource-limited countries, a large number of patients have previously received (or continue to receive) d4T, and many have developed peripheral neuropathy. The identification of genetic predictors of increased risk might suggest novel therapeutic targets for such patients. In AIDS Clinical Trials Group protocol 384, antiretroviral-naïve patients were randomized to d4T/didanosine (ddI)- or zidovudine/lamivudine-containing regimens. Data from d4T/ddI recipients were analyzed for genome-wide associations (approximately 1 million genetic loci) with new onset distal sensory peripheral neuropathy. Analyses involved 254 patients (49 % White, 34 % Black, 17 % Hispanic), comprising 90 peripheral neuropathy cases (32 grade 1, 35 grade 2, 23 grade 3) and 164 controls. After correcting for multiple comparisons, no polymorphism was consistently associated with neuropathy among all patients, among White, Black, and Hispanic patients analyzed separately, both in genome-wide analyses (threshold, P < 5.0 × 10(-8)) and focused on 46 neuropathy-associated genes (threshold, P < 3.5 × 10(-5)). In the latter analyses, the lowest P values were in KIF1A among Whites (rs10199388, P = 8.4 × 10(-4)), in LITAF among Blacks (rs13333308, P = 6.0 × 10(-6)), and in NEFL among Hispanics (rs17763685, P = 5.6 × 10(-6)). Susceptibility to d4T/ddI-associated neuropathy is not explained by a single genetic variant with a marked effect.
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04/07/2014 16:42
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20/08/2019 14:49
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