{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:29:17Z","timestamp":1785320957895,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>We have identified rheumatoid arthritis (RA) risk\u2010associated single nucleotide polymorphisms (SNPs) in the mitochondrial displacement loop (D\u2010loop) including the major alleles of nucleotides 195T\/C, 16260C\/T, and 16519C\/T as well as the minor alleles of nucleotides 146T\/C and 150C\/T previously.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We evaluated the potential relationships of these SNPs with status for oxidative stress and inflammation cytokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The DNA was extracted from blood samples of RA patients, and the SNPs of DNA D\u2010loop were verified by polymerase chain reaction amplification and sequence analysis. Serum levels of inflammatory cytokines including interferon\u2010\u03b3 (IFN\u2010\u03b3), interleukin\u20102 (IL\u20102), IL\u20106, IL\u201010, and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) were determined by cytometric bead array. Plasma reactive oxygen species (ROS) levels were measured by fluorescent probe technology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The RA risk\u2010related allele <jats:italic>16519C<\/jats:italic> was significantly associated with high IFN\u2010\u03b3 levels (100.576\u2009\u00b1\u200911.769 vs 64.268\u2009\u00b1\u20098.199, 95% confidence interval [CI] \u201366.317 to \u20136.299, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.018). This allele also associated with ROS at borderline statistics level (619.295\u2009\u00b1\u200936.687 vs 526.979\u2009\u00b1\u200925.896, 95% CI \u2013186.145 to \u20131.513, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.054). The subsequent analysis also showed that the ROS levels were positively correlated with IFN\u2010\u03b3 levels (<jats:italic>R<\/jats:italic>\u00a0=\u00a00.291, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.002). Further analysis showed that RA patients with high C\u2010reactive protein levels displayed a higher ROS level (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results imply that the <jats:italic>16519C<\/jats:italic> allele of the mtDNA D\u2010loop might promote ROS and IFN\u2010\u03b3 levels by altering the replication and transcription of mtDNA, thereby modifying RA development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Remark<\/jats:title><jats:p>The potential relationships of RA\u2010associated SNPs in the mitochondrial D\u2010loop with status for oxidative stress and inflammation were evaluated. The <jats:italic>16519C<\/jats:italic> allele of the mtDNA D\u2010loop might promote ROS and IFN\u2010\u03b3 levels by altering the replication and transcription of mtDNA to modify RA development.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.14465","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T01:11:57Z","timestamp":1666055517000},"page":"124-131","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Risk\u2010associated single nucleotide polymorphisms of mitochondrial D\u2010loop mediate imbalance of cytokines and redox in rheumatoid arthritis"],"prefix":"10.1111","volume":"26","author":[{"given":"Jingnan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Hematology The Second Hospital of Hebei Medical University  Shijiazhuang 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