title: Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients.
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; R (2) = 0.19) or haplotypes (model p < 0.0001; R (2) = 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.
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
authors.forename: Hayley
authors.initials: H
authors.lastname: Goullee
authors.affiliation: Brain Function Research Group, School of Physiology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Antonia L
authors.initials: AL
authors.lastname: Wadley
authors.affiliation: Brain Function Research Group, School of Physiology, University of the Witwatersrand, Johannesburg, South Africa.|Department of Infectious Diseases, Alfred Hospital and Monash University, and Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Cherry
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
authors.forename: Richard J N
authors.initials: RJ
authors.lastname: Allcock
authors.affiliation: Centre for Comparative Genomics, Murdoch University, Perth, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Black
authors.affiliation: Brain Function Research Group, School of Physiology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Kamerman
authors.affiliation: Brain Function Research Group, School of Physiology, University of the Witwatersrand, Johannesburg, South Africa. patricia.price@curtin.edu.au.|School of Biomedical Science, Curtin University of Technology, Bentley, Western Australia, 6845, Australia. patricia.price@curtin.edu.au.
authors.forename: Patricia
authors.identifier: 0000-0003-3078-4451
authors.initials: P
authors.lastname: Price
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D044383:Black People; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011115:Polyneuropathies / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D011379:Prognosis; D058848:Receptors, Purinergic P2X4 / Q000235:genetics / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism; D013019:South Africa; D018119:Stavudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; C546468:P2RX7 protein, human; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7; D018119:Stavudine; C517698:CAMKK2 protein, human; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase
keywords: CAMKK2; HIV; P2X4R; P2X7R; Sensory neuropathy