Genetic variation in iron metabolism is associated with neuropathic pain and pain severity in HIV-infected patients on antiretroviral therapy.
HIV sensory neuropathy and distal neuropathic pain (DNP) are common, disabling complications associated with combination antiretroviral therapy (cART). We previously associated iron-regulatory genetic polymorphisms with a reduced risk of HIV sensory neuropathy during more neurotoxic types of cART. W...
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2014
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oai:doaj.org-article:b6001d46828e41dc99eca8d1e55d15d32021-11-25T06:03:43ZGenetic variation in iron metabolism is associated with neuropathic pain and pain severity in HIV-infected patients on antiretroviral therapy.1932-620310.1371/journal.pone.0103123https://doaj.org/article/b6001d46828e41dc99eca8d1e55d15d32014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25144566/?tool=EBIhttps://doaj.org/toc/1932-6203HIV sensory neuropathy and distal neuropathic pain (DNP) are common, disabling complications associated with combination antiretroviral therapy (cART). We previously associated iron-regulatory genetic polymorphisms with a reduced risk of HIV sensory neuropathy during more neurotoxic types of cART. We here evaluated the impact of polymorphisms in 19 iron-regulatory genes on DNP in 560 HIV-infected subjects from a prospective, observational study, who underwent neurological examinations to ascertain peripheral neuropathy and structured interviews to ascertain DNP. Genotype-DNP associations were explored by logistic regression and permutation-based analytical methods. Among 559 evaluable subjects, 331 (59%) developed HIV-SN, and 168 (30%) reported DNP. Fifteen polymorphisms in 8 genes (p<0.05) and 5 variants in 4 genes (p<0.01) were nominally associated with DNP: polymorphisms in TF, TFRC, BMP6, ACO1, SLC11A2, and FXN conferred reduced risk (adjusted odds ratios [ORs] ranging from 0.2 to 0.7, all p<0.05); other variants in TF, CP, ACO1, BMP6, and B2M conferred increased risk (ORs ranging from 1.3 to 3.1, all p<0.05). Risks associated with some variants were statistically significant either in black or white subgroups but were consistent in direction. ACO1 rs2026739 remained significantly associated with DNP in whites (permutation p<0.0001) after correction for multiple tests. Several of the same iron-regulatory-gene polymorphisms, including ACO1 rs2026739, were also associated with severity of DNP (all p<0.05). Common polymorphisms in iron-management genes are associated with DNP and with DNP severity in HIV-infected persons receiving cART. Consistent risk estimates across population subgroups and persistence of the ACO1 rs2026739 association after adjustment for multiple testing suggest that genetic variation in iron-regulation and transport modulates susceptibility to DNP.Asha R KallianpurPeilin JiaRonald J EllisZhongming ZhaoCinnamon BlossWanqing WenChristina M MarraTodd HulganDavid M SimpsonSusan MorgelloJustin C McArthurDavid B CliffordAnn C CollierBenjamin B GelmanJ Allen McCutchanDonald FranklinDavid C SamuelsDebralee RosarioEmily HolzingerDeborah G MurdockScott LetendreIgor GrantCHARTER Study GroupPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e103123 (2014) |
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Medicine R Science Q |
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Medicine R Science Q Asha R Kallianpur Peilin Jia Ronald J Ellis Zhongming Zhao Cinnamon Bloss Wanqing Wen Christina M Marra Todd Hulgan David M Simpson Susan Morgello Justin C McArthur David B Clifford Ann C Collier Benjamin B Gelman J Allen McCutchan Donald Franklin David C Samuels Debralee Rosario Emily Holzinger Deborah G Murdock Scott Letendre Igor Grant CHARTER Study Group Genetic variation in iron metabolism is associated with neuropathic pain and pain severity in HIV-infected patients on antiretroviral therapy. |
| description |
HIV sensory neuropathy and distal neuropathic pain (DNP) are common, disabling complications associated with combination antiretroviral therapy (cART). We previously associated iron-regulatory genetic polymorphisms with a reduced risk of HIV sensory neuropathy during more neurotoxic types of cART. We here evaluated the impact of polymorphisms in 19 iron-regulatory genes on DNP in 560 HIV-infected subjects from a prospective, observational study, who underwent neurological examinations to ascertain peripheral neuropathy and structured interviews to ascertain DNP. Genotype-DNP associations were explored by logistic regression and permutation-based analytical methods. Among 559 evaluable subjects, 331 (59%) developed HIV-SN, and 168 (30%) reported DNP. Fifteen polymorphisms in 8 genes (p<0.05) and 5 variants in 4 genes (p<0.01) were nominally associated with DNP: polymorphisms in TF, TFRC, BMP6, ACO1, SLC11A2, and FXN conferred reduced risk (adjusted odds ratios [ORs] ranging from 0.2 to 0.7, all p<0.05); other variants in TF, CP, ACO1, BMP6, and B2M conferred increased risk (ORs ranging from 1.3 to 3.1, all p<0.05). Risks associated with some variants were statistically significant either in black or white subgroups but were consistent in direction. ACO1 rs2026739 remained significantly associated with DNP in whites (permutation p<0.0001) after correction for multiple tests. Several of the same iron-regulatory-gene polymorphisms, including ACO1 rs2026739, were also associated with severity of DNP (all p<0.05). Common polymorphisms in iron-management genes are associated with DNP and with DNP severity in HIV-infected persons receiving cART. Consistent risk estimates across population subgroups and persistence of the ACO1 rs2026739 association after adjustment for multiple testing suggest that genetic variation in iron-regulation and transport modulates susceptibility to DNP. |
| format |
article |
| author |
Asha R Kallianpur Peilin Jia Ronald J Ellis Zhongming Zhao Cinnamon Bloss Wanqing Wen Christina M Marra Todd Hulgan David M Simpson Susan Morgello Justin C McArthur David B Clifford Ann C Collier Benjamin B Gelman J Allen McCutchan Donald Franklin David C Samuels Debralee Rosario Emily Holzinger Deborah G Murdock Scott Letendre Igor Grant CHARTER Study Group |
| author_facet |
Asha R Kallianpur Peilin Jia Ronald J Ellis Zhongming Zhao Cinnamon Bloss Wanqing Wen Christina M Marra Todd Hulgan David M Simpson Susan Morgello Justin C McArthur David B Clifford Ann C Collier Benjamin B Gelman J Allen McCutchan Donald Franklin David C Samuels Debralee Rosario Emily Holzinger Deborah G Murdock Scott Letendre Igor Grant CHARTER Study Group |
| author_sort |
Asha R Kallianpur |
| title |
Genetic variation in iron metabolism is associated with neuropathic pain and pain severity in HIV-infected patients on antiretroviral therapy. |
| title_short |
Genetic variation in iron metabolism is associated with neuropathic pain and pain severity in HIV-infected patients on antiretroviral therapy. |
| title_full |
Genetic variation in iron metabolism is associated with neuropathic pain and pain severity in HIV-infected patients on antiretroviral therapy. |
| title_fullStr |
Genetic variation in iron metabolism is associated with neuropathic pain and pain severity in HIV-infected patients on antiretroviral therapy. |
| title_full_unstemmed |
Genetic variation in iron metabolism is associated with neuropathic pain and pain severity in HIV-infected patients on antiretroviral therapy. |
| title_sort |
genetic variation in iron metabolism is associated with neuropathic pain and pain severity in hiv-infected patients on antiretroviral therapy. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/b6001d46828e41dc99eca8d1e55d15d3 |
| work_keys_str_mv |
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