Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients

Hayley Goullee, A.L. Wadley, C.L. Cherry, Richard J.N. Allcock, M. Black, P.R. Kamerman, P. Price

    Research output: Contribution to journalArticle

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    Abstract

    © 2016, Journal of NeuroVirology, Inc.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.
    Original languageEnglish
    Pages (from-to)508-517
    Number of pages10
    JournalJournal of NeuroVirology
    Volume22
    Issue number4
    DOIs
    Publication statusPublished - 2016

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    HIV
    Haplotypes
    Single Nucleotide Polymorphism
    Logistic Models
    Stavudine
    Peripheral Nervous System Diseases
    Multigene Family
    Fluorescent Dyes
    Signs and Symptoms
    Genotype
    Demography
    Pathology
    Viruses
    Inflammation
    DNA
    Genes
    Therapeutics

    Cite this

    Goullee, H., Wadley, A. L., Cherry, C. L., Allcock, R. J. N., Black, M., Kamerman, P. R., & Price, P. (2016). Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients. Journal of NeuroVirology, 22(4), 508-517. https://doi.org/10.1007/s13365-015-0421-4
    Goullee, Hayley ; Wadley, A.L. ; Cherry, C.L. ; Allcock, Richard J.N. ; Black, M. ; Kamerman, P.R. ; Price, P. / Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients. In: Journal of NeuroVirology. 2016 ; Vol. 22, No. 4. pp. 508-517.
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    abstract = "{\circledC} 2016, Journal of NeuroVirology, Inc.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.",
    author = "Hayley Goullee and A.L. Wadley and C.L. Cherry and Allcock, {Richard J.N.} and M. Black and P.R. Kamerman and P. Price",
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    Goullee, H, Wadley, AL, Cherry, CL, Allcock, RJN, Black, M, Kamerman, PR & Price, P 2016, 'Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients' Journal of NeuroVirology, vol. 22, no. 4, pp. 508-517. https://doi.org/10.1007/s13365-015-0421-4

    Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients. / Goullee, Hayley; Wadley, A.L.; Cherry, C.L.; Allcock, Richard J.N.; Black, M.; Kamerman, P.R.; Price, P.

    In: Journal of NeuroVirology, Vol. 22, No. 4, 2016, p. 508-517.

    Research output: Contribution to journalArticle

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    AU - Goullee, Hayley

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    AU - Cherry, C.L.

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    AU - Black, M.

    AU - Kamerman, P.R.

    AU - Price, P.

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    N2 - © 2016, Journal of NeuroVirology, Inc.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.

    AB - © 2016, Journal of NeuroVirology, Inc.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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