Abstract
Relatively little research has been done in recent years to understand what leads to the unceasingly high rates of HIV sensory neuropathy despite successful antiretroviral treatment. In vivo and in vitro studies demonstrate neuronal damage induced by HIV and increasingly identified ART neurotoxicity involving mitochondrial dysfunction and innate immune system activation in peripheral nerves, ultimately all pathways resulting in enhanced pro-inflammatory cytokine secretion. Furthermore, many infectious/autoimmune/malignant diseases are influenced by the production-profile of pro-inflammatory and anti-inflammatory cytokines, due to inter-individual allelic polymorphism within cytokine gene regulatory regions. Associations of cytokine gene polymorphisms are investigated with the aim of identifying potential genetic markers for susceptibility to HIV peripheral neuropathy including ART-dependent toxic neuropathy. One hundred seventy-one people living with HIV in Northern Greece, divided into two sub-groups according to the presence/absence of peripheral neuropathy, were studied over a 5-year period. Diagnosis was based on the Brief Peripheral Neuropathy Screening. Cytokine genoty** was performed by sequence-specific primer-polymerase chain reaction. Present study findings identify age as an important risk factor (p < 0.01) and support the idea that cytokine gene polymorphisms are at least involved in HIV peripheral-neuropathy pathogenesis. Specifically, carriers of IL1a-889/rs1800587 TT genotype and IL4-1098/rs2243250 GG genotype disclosed greater relative risk for develo** HIV peripheral neuropathy (OR: 2.9 and 7.7 respectively), while conversely, carriers of IL2+166/rs2069763 TT genotype yielded lower probability (OR: 3.1), all however, with marginal statistical significance. The latter, if confirmed in a larger Greek population cohort, may offer in the future novel genetic markers to identify susceptibility, while it remains significant that further ethnicity-oriented studies continue to be conducted in a similar pursuit.
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The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials. More information can be available upon request from the corresponding author, [IN].
Notes
The Hardy-Weinberg equilibrium test was valid for both groups.
The Hardy-Weinberg equilibrium test did not apply to both groups.
The Hardy-Weinberg equilibrium test was valid for the PN- group, and did not apply to the PN+ group.
The Hardy-Weinberg equilibrium test was valid for the PN+ group, and did not apply to the PN- group.
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The present study is pertinent to the first author’s doctoral dissertation. The first author would like to express appreciation to Prof Emeritus Dimitrios Manousakis-Karakostas and Prof. Emeritus. Nikolaos Taskos, as former Heads of the 2nd Department of Neurology of Aristotle University of Thessaloniki – School of Medicine. We would also like to extend our thanks to the anonymous reviewers and the editor, who, with their academic experience, have provided us with valuable ideas, recommendations, advice, and solutions and have motivated us to improve.
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Nikolaidis, I., Karakasi, M., Pilalas, D. et al. Association of cytokine gene polymorphisms with peripheral neuropathy susceptibility in people living with HIV in Greece. J. Neurovirol. 29, 626–639 (2023). https://doi.org/10.1007/s13365-023-01169-5
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DOI: https://doi.org/10.1007/s13365-023-01169-5