Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients

HIV-associated sensory neuropathy (HIV-SN) is the most common neurological condition associated with HIV. HIV-SN has characteristics of an inflammatory pathology caused by the virus itself and/or by antiretroviral treatment (ART). Here, we assess the impact of single-nucleotide polymorphisms (SNPs)...

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Main Authors: Goullee, H., Wadley, A., Cherry, C., Allcock, R., Black, M., Kamerman, P., Price, Patricia
Format: Journal Article
Published: Springer 2016
Online Access:http://hdl.handle.net/20.500.11937/10666
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author Goullee, H.
Wadley, A.
Cherry, C.
Allcock, R.
Black, M.
Kamerman, P.
Price, Patricia
author_facet Goullee, H.
Wadley, A.
Cherry, C.
Allcock, R.
Black, M.
Kamerman, P.
Price, Patricia
author_sort Goullee, H.
building Curtin Institutional Repository
collection Online Access
description HIV-associated sensory neuropathy (HIV-SN) is the most common neurological condition associated with HIV. HIV-SN has characteristics of an inflammatory pathology caused by the virus itself and/or by antiretroviral treatment (ART). Here, we assess the impact of single-nucleotide polymorphisms (SNPs) in a cluster of three genes that affect inflammation and neuronal repair: P2X7R, P2X4R and CAMKK2. HIV-SN status was assessed using the Brief Peripheral Neuropathy Screening tool, with SN defined by bilateral symptoms and signs. Forty-five SNPs in P2X7R, P2X4R and CAMKK2 were genotyped using TaqMan fluorescent probes, in DNA samples from 153 HIV+ black Southern African patients exposed to stavudine. Haplotypes were derived using the fastPHASE algorithm, and SNP genotypes and haplotypes associated with HIV-SN were identified. Optimal logistic regression models included demographics (age and height), with SNPs (model p < 0.0001; R2 = 0.19) or haplotypes (model p < 0.0001; R2 = 0.18, n = 137 excluding patients carrying CAMKK2 haplotypes perfectly associated with SN). Overall, CAMKK2 exhibited the strongest associations with HIV-SN, with two SNPs and six haplotypes predicting SN status in black Southern Africans. This gene warrants further study.
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spelling curtin-20.500.11937-106662019-02-19T05:34:46Z Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients Goullee, H. Wadley, A. Cherry, C. Allcock, R. Black, M. Kamerman, P. Price, Patricia HIV-associated sensory neuropathy (HIV-SN) is the most common neurological condition associated with HIV. HIV-SN has characteristics of an inflammatory pathology caused by the virus itself and/or by antiretroviral treatment (ART). Here, we assess the impact of single-nucleotide polymorphisms (SNPs) in a cluster of three genes that affect inflammation and neuronal repair: P2X7R, P2X4R and CAMKK2. HIV-SN status was assessed using the Brief Peripheral Neuropathy Screening tool, with SN defined by bilateral symptoms and signs. Forty-five SNPs in P2X7R, P2X4R and CAMKK2 were genotyped using TaqMan fluorescent probes, in DNA samples from 153 HIV+ black Southern African patients exposed to stavudine. Haplotypes were derived using the fastPHASE algorithm, and SNP genotypes and haplotypes associated with HIV-SN were identified. Optimal logistic regression models included demographics (age and height), with SNPs (model p < 0.0001; R2 = 0.19) or haplotypes (model p < 0.0001; R2 = 0.18, n = 137 excluding patients carrying CAMKK2 haplotypes perfectly associated with SN). Overall, CAMKK2 exhibited the strongest associations with HIV-SN, with two SNPs and six haplotypes predicting SN status in black Southern Africans. This gene warrants further study. 2016 Journal Article http://hdl.handle.net/20.500.11937/10666 10.1007/s13365-015-0421-4 Springer fulltext
spellingShingle Goullee, H.
Wadley, A.
Cherry, C.
Allcock, R.
Black, M.
Kamerman, P.
Price, Patricia
Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients
title Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients
title_full Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients
title_fullStr Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients
title_full_unstemmed Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients
title_short Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients
title_sort polymorphisms in camkk2 may predict sensory neuropathy in african hiv patients
url http://hdl.handle.net/20.500.11937/10666