Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients

Hayley Goullee, Antonia L. Wadley, Catherine L. Cherry, Richard J N Allcock, Michael A Black, Peter R. Kamerman, Patricia Price

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21 Citations (Scopus)

Abstract

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 - 1 Aug 2016

Keywords

  • CAMKK2
  • HIV
  • P2X4R
  • P2X7R
  • Sensory neuropathy

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