TNF Block Gene Variants Associate with Pain Intensity in Black Southern Africans with HIV-associated Sensory Neuropathy

L.M. Hendry, A.L. Wadley, C.L. Cherry, Patricia Price, Z. Lombard, P.R. Kamerman

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    © 2015 Wolters Kluwer Health, Inc. All rights reserved. Objectives: HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection, and it is often painful. Tumor necrosis factor (TNF)-α is implicated in neuropathic pain, but associations between neuropathic pain and polymorphisms in the TNFA gene have not been identified. The "TNF block" is a region of high linkage disequilibrium within the central major histocompatability complex that contains several genes involved in the regulation of inflammation, including TNFA. Polymorphisms in the block have been associated with an altered risk of HIV-SN, but no investigations into whether this region is associated with the painful symptoms of neuropathy have been undertaken. Therefore, we investigated whether polymorphisms in the TNF block are associated with pain intensity in black Southern Africans with HIV-SN. Methods: Single-nucleotide polymorphisms (SNPs) defining TNF block haplotypes and African-specific tagSNPs were genotyped in samples from 150 black Southern Africans with HIV-SN. Results: One SNP allele, rs28445017∗A, was significantly associated with an increased pain intensity after correction for age, sex, and the CD4 T-cell count. A common 3-SNP haplotype containing rs28445017∗G remained associated with a reduced pain intensity after correction for covariates and multiple comparisons. Discussion: We identified a novel genetic association between polymorphisms in the TNF block and the pain intensity in black Southern Africans with HIV-SN. Our study implicates rs28445017 in painful HIV-SN, although its precise role and whether it may be causative is unclear. rs28445017 was not associated with the risk for HIV-SN as such, highlighting potential differences between the pathophysiology of the neuropathy and the painful features of the neuropathy.
    Original languageEnglish
    Pages (from-to)45-50
    JournalClinical Journal of Pain
    Volume32
    Issue number1
    DOIs
    Publication statusPublished - 2016

    Fingerprint

    Tumor Necrosis Factor-alpha
    HIV
    Pain
    Genes
    Single Nucleotide Polymorphism
    Neuralgia
    Haplotypes
    Linkage Disequilibrium
    CD4 Lymphocyte Count
    HIV Infections
    Alleles
    Inflammation
    T-Lymphocytes
    Health
    Painful Neuropathy

    Cite this

    Hendry, L.M. ; Wadley, A.L. ; Cherry, C.L. ; Price, Patricia ; Lombard, Z. ; Kamerman, P.R. / TNF Block Gene Variants Associate with Pain Intensity in Black Southern Africans with HIV-associated Sensory Neuropathy. In: Clinical Journal of Pain. 2016 ; Vol. 32, No. 1. pp. 45-50.
    @article{ea355949578a4a76b2b7d6bc3579c16c,
    title = "TNF Block Gene Variants Associate with Pain Intensity in Black Southern Africans with HIV-associated Sensory Neuropathy",
    abstract = "{\circledC} 2015 Wolters Kluwer Health, Inc. All rights reserved. Objectives: HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection, and it is often painful. Tumor necrosis factor (TNF)-α is implicated in neuropathic pain, but associations between neuropathic pain and polymorphisms in the TNFA gene have not been identified. The {"}TNF block{"} is a region of high linkage disequilibrium within the central major histocompatability complex that contains several genes involved in the regulation of inflammation, including TNFA. Polymorphisms in the block have been associated with an altered risk of HIV-SN, but no investigations into whether this region is associated with the painful symptoms of neuropathy have been undertaken. Therefore, we investigated whether polymorphisms in the TNF block are associated with pain intensity in black Southern Africans with HIV-SN. Methods: Single-nucleotide polymorphisms (SNPs) defining TNF block haplotypes and African-specific tagSNPs were genotyped in samples from 150 black Southern Africans with HIV-SN. Results: One SNP allele, rs28445017∗A, was significantly associated with an increased pain intensity after correction for age, sex, and the CD4 T-cell count. A common 3-SNP haplotype containing rs28445017∗G remained associated with a reduced pain intensity after correction for covariates and multiple comparisons. Discussion: We identified a novel genetic association between polymorphisms in the TNF block and the pain intensity in black Southern Africans with HIV-SN. Our study implicates rs28445017 in painful HIV-SN, although its precise role and whether it may be causative is unclear. rs28445017 was not associated with the risk for HIV-SN as such, highlighting potential differences between the pathophysiology of the neuropathy and the painful features of the neuropathy.",
    author = "L.M. Hendry and A.L. Wadley and C.L. Cherry and Patricia Price and Z. Lombard and P.R. Kamerman",
    year = "2016",
    doi = "10.1097/AJP.0000000000000224",
    language = "English",
    volume = "32",
    pages = "45--50",
    journal = "The Clinical Journal of Pain",
    issn = "0749-8047",
    publisher = "Lippincott Williams & Wilkins",
    number = "1",

    }

    TNF Block Gene Variants Associate with Pain Intensity in Black Southern Africans with HIV-associated Sensory Neuropathy. / Hendry, L.M.; Wadley, A.L.; Cherry, C.L.; Price, Patricia; Lombard, Z.; Kamerman, P.R.

    In: Clinical Journal of Pain, Vol. 32, No. 1, 2016, p. 45-50.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - TNF Block Gene Variants Associate with Pain Intensity in Black Southern Africans with HIV-associated Sensory Neuropathy

    AU - Hendry, L.M.

    AU - Wadley, A.L.

    AU - Cherry, C.L.

    AU - Price, Patricia

    AU - Lombard, Z.

    AU - Kamerman, P.R.

    PY - 2016

    Y1 - 2016

    N2 - © 2015 Wolters Kluwer Health, Inc. All rights reserved. Objectives: HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection, and it is often painful. Tumor necrosis factor (TNF)-α is implicated in neuropathic pain, but associations between neuropathic pain and polymorphisms in the TNFA gene have not been identified. The "TNF block" is a region of high linkage disequilibrium within the central major histocompatability complex that contains several genes involved in the regulation of inflammation, including TNFA. Polymorphisms in the block have been associated with an altered risk of HIV-SN, but no investigations into whether this region is associated with the painful symptoms of neuropathy have been undertaken. Therefore, we investigated whether polymorphisms in the TNF block are associated with pain intensity in black Southern Africans with HIV-SN. Methods: Single-nucleotide polymorphisms (SNPs) defining TNF block haplotypes and African-specific tagSNPs were genotyped in samples from 150 black Southern Africans with HIV-SN. Results: One SNP allele, rs28445017∗A, was significantly associated with an increased pain intensity after correction for age, sex, and the CD4 T-cell count. A common 3-SNP haplotype containing rs28445017∗G remained associated with a reduced pain intensity after correction for covariates and multiple comparisons. Discussion: We identified a novel genetic association between polymorphisms in the TNF block and the pain intensity in black Southern Africans with HIV-SN. Our study implicates rs28445017 in painful HIV-SN, although its precise role and whether it may be causative is unclear. rs28445017 was not associated with the risk for HIV-SN as such, highlighting potential differences between the pathophysiology of the neuropathy and the painful features of the neuropathy.

    AB - © 2015 Wolters Kluwer Health, Inc. All rights reserved. Objectives: HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection, and it is often painful. Tumor necrosis factor (TNF)-α is implicated in neuropathic pain, but associations between neuropathic pain and polymorphisms in the TNFA gene have not been identified. The "TNF block" is a region of high linkage disequilibrium within the central major histocompatability complex that contains several genes involved in the regulation of inflammation, including TNFA. Polymorphisms in the block have been associated with an altered risk of HIV-SN, but no investigations into whether this region is associated with the painful symptoms of neuropathy have been undertaken. Therefore, we investigated whether polymorphisms in the TNF block are associated with pain intensity in black Southern Africans with HIV-SN. Methods: Single-nucleotide polymorphisms (SNPs) defining TNF block haplotypes and African-specific tagSNPs were genotyped in samples from 150 black Southern Africans with HIV-SN. Results: One SNP allele, rs28445017∗A, was significantly associated with an increased pain intensity after correction for age, sex, and the CD4 T-cell count. A common 3-SNP haplotype containing rs28445017∗G remained associated with a reduced pain intensity after correction for covariates and multiple comparisons. Discussion: We identified a novel genetic association between polymorphisms in the TNF block and the pain intensity in black Southern Africans with HIV-SN. Our study implicates rs28445017 in painful HIV-SN, although its precise role and whether it may be causative is unclear. rs28445017 was not associated with the risk for HIV-SN as such, highlighting potential differences between the pathophysiology of the neuropathy and the painful features of the neuropathy.

    U2 - 10.1097/AJP.0000000000000224

    DO - 10.1097/AJP.0000000000000224

    M3 - Article

    VL - 32

    SP - 45

    EP - 50

    JO - The Clinical Journal of Pain

    JF - The Clinical Journal of Pain

    SN - 0749-8047

    IS - 1

    ER -