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

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About: Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384 Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384
Creator	Li, Jun Johnson, Daniel Li, J Johnson, D Robbins, Gregory Clifford, D Clifford, David Haas, D Haas, David Leger, P Leger, Paul Mclaren, P Mclaren, Paul Robbins, G Shafer, R Shafer, Robert
Source	PMC
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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13365-014-0235-9) contains supplementary material, which is available to authorized users.
has issue date	2014-02-20(xsd:dateTime)
bibo:doi	10.1007/s13365-014-0235-9
bibo:pmid	24554482
has license	no-cc
sha1sum (hex)	cd37758a04be1b3086acec23bd79b2358ba09105
schema:url	https://doi.org/10.1007/s13365-014-0235-9
resource representing a document's title	Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384
has PubMed Central identifier	PMC4114519
has PubMed identifier	24554482
schema:publication	J Neurovirol
resource representing a document's body	covid:cd37758a04be1b3086acec23bd79b2358ba09105#body_text
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