{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T06:11:52Z","timestamp":1760076712489,"version":"build-2065373602"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The present study aimed to investigate the association of the <jats:italic>ATP-binding cassette subfamily B member 1 (ABCB1) 3435C\/T<\/jats:italic> and <jats:italic>methylenetetrahydrofolate reductase (MTHFR) 677C\/T<\/jats:italic> and <jats:italic>1298A\/C<\/jats:italic> polymorphisms with susceptibility to RA and RA subtype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We enrolled 85 RA patients and 45 healthy individuals in this study. Genotyping for <jats:italic>ABCB1 3435C\/T<\/jats:italic>, <jats:italic>MTHFR 677C\/T<\/jats:italic> and <jats:italic>1298A\/C<\/jats:italic> was performed using fluorescence <jats:italic>in situ<\/jats:italic> hybridization technology (FISH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No significant differences in the genotype and allele frequency distributions of <jats:italic>ABCB1 3435C\/T<\/jats:italic>, <jats:italic>MTHFR 1298A\/C<\/jats:italic> or <jats:italic>MTHFR677C\/T<\/jats:italic> were detected between patients with RA and healthy individuals (<jats:italic>p\u202f&amp;gt;\u202f0.05<\/jats:italic>). Logistic regression analysis, after adjusting for sex and age, showed that the <jats:italic>MTHFR677C\/T TT<\/jats:italic> genotype was associated with increased susceptibility to RA compared with the <jats:italic>CC<\/jats:italic> genotype (<jats:italic>TT versus CC<\/jats:italic>, <jats:italic>p\u202f=\u202f0.034<\/jats:italic>, OR\u202f=\u202f2.316; 95%CI\u202f=\u202f1.067\u20135.029); however, after Bonferroni correction, the association between the MTHFR677C\/T TT genotype and RA susceptibility was no longer significant. That <jats:italic>MTHFR 677C\/T<\/jats:italic> genotype frequency (<jats:italic>CT versus CC<\/jats:italic>, <jats:italic>p\u202f=\u202f0.040<\/jats:italic>, OR\u202f=\u202f6.504; 95% CI\u202f=\u202f1.087\u201338.935) and dominant model (<jats:italic>CT+TT versus CC<\/jats:italic>, <jats:italic>p\u202f=\u202f0.025<\/jats:italic>, OR\u202f=\u202f6.556; 95% CI\u202f=\u202f1.272\u201333.799) was associated with ACPA status among RA patients; and that <jats:italic>MTHFR 677C\/T<\/jats:italic> genotype frequency (<jats:italic>TT versus CC<\/jats:italic>, <jats:italic>p\u202f=\u202f0.044<\/jats:italic>, OR\u202f=\u202f2.171; 95% CI\u202f=\u202f1.020\u20134.623) and codominant model (<jats:italic>CC versus CT versus TT<\/jats:italic>, <jats:italic>p\u202f=\u202f0.026<\/jats:italic>, OR\u202f=\u202f2.059; 95% CI\u202f=\u202f1.089\u20133.891) were associated with RF status among RA patients; Similarly, the associations observed in ACPA-positive and RF-positive subgroups also lost significance after Bonferroni correction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The <jats:italic>MTHFR 677C\/T<\/jats:italic> polymorphism may be associated with susceptibility to RA and RA subtypes; <jats:italic>ABCB1 3435C\/T<\/jats:italic> and <jats:italic>MTHFR 1298A\/C<\/jats:italic> were not associated with the susceptibility to RA or RA subtypes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1660473","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T05:29:05Z","timestamp":1760074145000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of ABCB1 and MTHFR genetic polymorphisms with rheumatoid arthritis susceptibility in a Chinese population"],"prefix":"10.3389","volume":"12","author":[{"given":"Yanfei","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jirong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaomei","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"101477","DOI":"10.1016\/j.berh.2019.101477","article-title":"The 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