{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:47:45Z","timestamp":1793155665645,"version":"4.5.0"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008191","name":"Wings for Life - Spinal Cord Research Foundation","doi-asserted-by":"crossref","award":["223293"],"award-info":[{"award-number":["223293"]}],"id":[{"id":"10.13039\/100008191","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008191","name":"Wings for Life Spinal Cord Research Foundation","doi-asserted-by":"crossref","award":["223293"],"award-info":[{"award-number":["223293"]}],"id":[{"id":"10.13039\/100008191","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The \u03b17 neuronal nicotinic acetylcholine receptors (\u03b17nAChRs) are essential for anti-inflammatory responses. The human-specific <jats:italic>CHRFAM7A<\/jats:italic> gene and its 2bp deletion polymorphism (<jats:italic>\u03942bp<\/jats:italic> variant) encodes a structurally-deficient \u03b17nAChRs that may impact the anti-inflammatory function. We studied 45 spinal cord injury (SCI) patients for up to six weeks post SCI to investigate the role of the <jats:italic>\u03942bp<\/jats:italic> variant on multiple circulating inflammatory mediators and two outcome measures (neuropathic pain and risk of pressure ulcers). The patient\u2019s SCI were classified as either severe or mild. Missing values were imputed. Overall genetic effect was conducted with independent sample t-test and corrected with false discovery rate (FDR). Univariate analysis and regression analysis were applied to evaluate the <jats:italic>\u03942bp<\/jats:italic> effects on temporal variation of inflammatory mediators post SCI and their interaction with outcome measures. In severe SCI, the <jats:italic>\u03942bp<\/jats:italic> carriers showed higher levels of circulating inflammatory mediators than the <jats:italic>\u03942bp<\/jats:italic> non-carriers in TNF-\u03b1 (FDR = 9.6x10<jats:sup>-4<\/jats:sup>), IFN-\u03b3 (FDR = 1.3x10<jats:sup>-3<\/jats:sup>), IL-13 (FDR = 1.6x10<jats:sup>-3<\/jats:sup>), CCL11 (FDR = 2.1x10<jats:sup>-3<\/jats:sup>), IL-12p70 (FDR = 2.2x10<jats:sup>-3<\/jats:sup>), IL-8 (FDR = 2.2x10<jats:sup>-3<\/jats:sup>), CXCL10 (FDR = 3.1x10<jats:sup>-3<\/jats:sup>), CCL4 (FDR = 5.7x10<jats:sup>-3<\/jats:sup>), IL-12p40 (FDR = 7.1x10<jats:sup>-3<\/jats:sup>), IL-1b (FDR = 0.014), IL-15 (FDR = 0.024), and IL-2 (FDR = 0.037). IL-8 and CCL2 were negatively associated with days post injury (DPI) for the <jats:italic>\u03942bp<\/jats:italic> carriers (P = 2x10<jats:sup>-7<\/jats:sup> and P = 2x10<jats:sup>-8<\/jats:sup>, respectively) and IL-5 was positively associated with DPI for the <jats:italic>\u03942bp<\/jats:italic> non-carriers (P = 0.015). Neuropathic pain was marginally positively associated with IL-13 for the <jats:italic>\u03942bp<\/jats:italic> carriers (P = 0.056). In mild SCI, the <jats:italic>\u03942bp<\/jats:italic> carriers had lower circulating levels of IL-15 (FDR = 0.04) than the <jats:italic>\u03942bp<\/jats:italic> non-carriers. Temporal variation of inflammatory mediators post SCI was not associated with the <jats:italic>\u03942bp<\/jats:italic> variant. For the mild SCI <jats:italic>\u03942bp<\/jats:italic> carriers, risk of pressure ulcers was positively associated with circulating levels of IFN-\u03b3, CXCL10, and CCL4 and negatively associated with circulating levels of IL-12p70. These findings support an important role for the human-specific <jats:italic>CHRFAM7A \u03942bp<\/jats:italic> gene variant in modifying anti-inflammatory function of \u03b17nAChRs following SCI.<\/jats:p>","DOI":"10.1371\/journal.pone.0251110","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T17:58:13Z","timestamp":1620323893000},"page":"e0251110","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effect of CHRFAM7A \u03942bp gene variant on secondary inflammation after spinal cord 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P.","family":"Conley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoram","family":"Vodovotz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brienza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy K.","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Robbins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendolyn A.","family":"Sowa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert 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