Abstract
Human immunodeficiency virus (HIV)-associated cognitive disorders (HAND) is characterized by impaired motor and intellectual functions, as well as mood disorders. Brain-derived neurotrophic factor and its receptor TrkB (or NTRK2) mediate the efficacy of antidepressant drugs. Genomic studies of BDNF/TrkB have implicated common single-nucleotide polymorphisms in the pathology of depression. In the current study, we investigated whether single-nucleotide polymorphisms (SNPs) (rs1212171, rs1439050, rs1187352, rs1778933, rs1443445, rs3780645, rs2378672, and rs11140800) in the NTRK2 has a functional impact on depression in HIV-positive subjects. We have utilized the Central Nervous System (CNS) HIV Antiretroviral Therapy Effects Research (CHARTER) cohort. Our methods explored the univariate associations of these SNPs with clinical (current and lifetime) diagnosis of depression via chi-square. The distribution of alleles was significantly different for African-Americans and Caucasians (non-Hispanic) for several SNPs, so our regression analyses included both “statistical controls” for race group and models for each group separately. Finally, we applied a method of simultaneous analysis of associations, estimating the mutually shared information across a system of variables, separately by race group. Our results indicate that there is no significant association between clinical diagnosis of major depression and these SNPs for either race group in any analysis. However, we identified that the SNP associations varied by race group and sex.
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Acknowledgements
This work was supported by the National Institutes of Health grants AI117970 (District of Columbia Center for AIDS Research) to V.A., and NS079172 and NS074916 to I.M, and N01 MH22005, HHSN271201000036C, and HHSN271201000030C to the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER).
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VA designed experiments, contributed to data analysis, and co-wrote the manuscript; FY contributed to data analysis and manuscript writing; IM contributed to experimental design and manuscript writing; SLL contributed to experimental design and materials; RET designed experiments, contributed to data analysis, and co-wrote the manuscript. All authors read and approved the final version of the manuscript.
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Author Futoshi Yumoto was employed by company Resonate, Inc. All other authors declare no competing interests.
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Avdoshina, V., Yumoto, F., Mocchetti, I. et al. Race-Dependent Association of Single-Nucleotide Polymorphisms in TrkB Receptor in People Living with HIV and Depression. Neurotox Res 39, 1721–1731 (2021). https://doi.org/10.1007/s12640-021-00406-1
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DOI: https://doi.org/10.1007/s12640-021-00406-1