Polymorphisms in P2X4R and CAMKK2 may affect TNFα production: Implications for a role in HIV-associated sensory neuropathy.
Polymorphisms in P2X4R and CAMKK2 associate with susceptibility to HIV-associated sensory neuropathy (HIV-SN) - a condition likely mediated by TNFα. As single nucleotide polymorphisms (SNPs) and haplotypes of CAMKK2, and a neighbouring gene P2X4R, mark susceptibility to HIV-SN in South Africans living with HIV, we examined the relationship between P2X4R and CAMKK2 genotypes and TNFα production. Peripheral blood mononuclear cells from 129 healthy donors were stimulated with killed Escherichia coli, and concentrations of soluble TNFα were assessed. Their DNA was genotyped for 22 SNPs in P2X4R and CAMKK2. Three SNPs within P2X4R and two SNPs within CAMKK2 influenced concentrations of TNFα, but these SNP did not associate with risk for HIV-SN. This incongruence may reflect differences in P2X4R haplotypes present in Africans and Europeans. However some CAMKK2 haplotypes were found in both populations, so CAMKK2 polymorphisms may impact upon HIV-SN via effects of the protein on pathways other than TNFα.
['Gaff|Jessica|J|', 'Halstrom|Samuel|S|', 'Temple|Suzanna E L|SEL|', 'Baltic|Svetlana|S|', 'Kamerman|Peter|P|', 'Price|Patricia|P|']
D000328:Adult D044383:Blacks D001782:Blood Donors D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase D004926:Escherichia coli D015658:HIV Infections D006239:Haplotypes D064368:Healthy Volunteers D006801:Humans D007963:Leukocytes, Mononuclear D010523:Peripheral Nervous System Diseases D020641:Polymorphism, Single Nucleotide D058848:Receptors, Purinergic P2X4 D014409:Tumor Necrosis Factor-alpha D044465:Whites
P2X4R CAMKK2 TNFα production Genetic polymorphism HIV sensory neuropathy