{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:08:55Z","timestamp":1793210935797,"version":"4.5.0"},"reference-count":31,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cPrograma de Apoyo a la Mejora en las Condiciones de Producci\u00f3n de los Miembros del SNI y SNCA 2019\u20132025\u201d, and in part, by the grant \u201cPrograma de Impulso a la Investigaci\u00f3n (PIN) 2024-V\u201d (U.D.l.C.-M.) from the Universidad de Guadalajara"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Hypovitaminosis D has been associated with worse rheumatoid arthritis (RA) manifestations. Notably, different genetic studies have reported that approximately 65% of hypovitaminosis D can be partially explained using the presence of single-nucleotide variants (SNVs) in key genes involved in its metabolism. This study aimed to investigate the association and gene\u2013gene interactions of four SNVs in vitamin D metabolism genes, rs10741657 (CYP2R1), rs10877012 (CYP27B1), rs4809959 (CYP24A1), and rs731236 TaqI (VDR), with hypovitaminosis D, RA, and its clinical disease activity in a Mexican mestizo population. Methods: This study was conducted among females: 204 RA patients and 204 control subjects (CS). Vitamin D serum levels (calcidiol) were analyzed using ELISA, SNVs through allelic discrimination with TaqMan\u00ae probes, and were analyzed using a multifactor dimensionality reduction (MDR) method. Results: MDR analysis suggested that GG and TT genotypes of rs10877012 (CYP27B1) were linked to lower calcidiol levels, while the CT and CC genotypes of rs731236 TaqI (VDR) were associated with increased RA susceptibility and higher disease activity. Logistic regression confirmed that the GG genotype of rs10877012 (CYP27B1) was associated with hypovitaminosis D (OR = 1.8; CI: 1.1\u20133.0; p = 0.01), and the CT genotype of rs731236 TaqI (VDR) with RA (OR = 1.9; CI: 1.2\u20132.9; p &lt; 0.01) and high DAS28-ESR (OR = 3.6; CI: 1.3\u201310.7; p &lt; 0.01). Conclusions: The GG genotype of rs10877012 CYP27B1 was associated with susceptibility to hypovitaminosis D, whereas the CT genotype of rs731236 TaqI VDR confers susceptibility to RA and high clinical disease activity in the Mexican mestizo population.<\/jats:p>","DOI":"10.3390\/genes16080967","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T07:56:06Z","timestamp":1755590166000},"page":"967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Interaction Between Vitamin D Metabolism Genetic Variants: Association with Hypovitaminosis D, Rheumatoid Arthritis, and Its Clinical Disease Activity"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1667-8794","authenticated-orcid":false,"given":"Bertha","family":"Campos-L\u00f3pez","sequence":"first","affiliation":[{"name":"Red de Inmunonutrici\u00f3n y Gen\u00f3mica Nutricional en las Enfermedades Autoinmunes; Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Instituto de Neurociencias Traslacionales, Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Doctorado en Ciencias en Biolog\u00eda Molecular en Medicina, Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9069-7478","authenticated-orcid":false,"given":"Melissa","family":"Rivera-Escoto","sequence":"additional","affiliation":[{"name":"Red de Inmunonutrici\u00f3n y Gen\u00f3mica Nutricional en las Enfermedades Autoinmunes; Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8993-6312","authenticated-orcid":false,"given":"Adolfo I.","family":"Ruiz-Ballesteros","sequence":"additional","affiliation":[{"name":"Red de Inmunonutrici\u00f3n y Gen\u00f3mica Nutricional en las Enfermedades Autoinmunes; Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6849-5965","authenticated-orcid":false,"given":"Karen","family":"Pesqueda-Cendejas","sequence":"additional","affiliation":[{"name":"Red de Inmunonutrici\u00f3n y Gen\u00f3mica Nutricional en las Enfermedades Autoinmunes; Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Instituto de Neurociencias Traslacionales, Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5452-6222","authenticated-orcid":false,"given":"Paulina E.","family":"Mora-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Red de Inmunonutrici\u00f3n y Gen\u00f3mica Nutricional en las Enfermedades Autoinmunes; Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Instituto de Neurociencias Traslacionales, Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4991-4965","authenticated-orcid":false,"given":"M\u00f3nica R.","family":"Meza-Meza","sequence":"additional","affiliation":[{"name":"Red de Inmunonutrici\u00f3n y Gen\u00f3mica Nutricional en las Enfermedades Autoinmunes; Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Instituto de Neurociencias Traslacionales, Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9213-8263","authenticated-orcid":false,"given":"Isela","family":"Parra-Rojas","sequence":"additional","affiliation":[{"name":"Red de Inmunonutrici\u00f3n y Gen\u00f3mica Nutricional en las Enfermedades Autoinmunes; Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Laboratorio de Investigaci\u00f3n en Obesidad y Diabetes, Facultad de Ciencias Qu\u00edmico-Biol\u00f3gicas, Universidad Aut\u00f3noma de Guerrero, Chilpancingo de los Bravo 39087, Guerrero, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7555-9851","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Moreno-Ort\u00edz","sequence":"additional","affiliation":[{"name":"Instituto de Gen\u00e9tica Humana \u201cDr. Enrique Corona Rivera\u201d, Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eneida","family":"Turij\u00e1n-Espinoza","sequence":"additional","affiliation":[{"name":"Red de Inmunonutrici\u00f3n y Gen\u00f3mica Nutricional en las Enfermedades Autoinmunes; Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Instituto de Neurociencias Traslacionales, Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Laboratorio de Inmunolog\u00eda y Biolog\u00eda Celular y Molecular, Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de San Luis Potosi, San Luis Potosi 78210, San Luis Potosi, Mexico"},{"name":"Departamento de Medicina Traslacional y Molecular, Centro de Investigaci\u00f3n en Ciencias de la Salud y Biomedicina (CICSaB), Universidad Aut\u00f3noma de San Luis Potosi, San Luis Potosi 78210, San Luis Potosi, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan M.","family":"Vargas-Morales","sequence":"additional","affiliation":[{"name":"Red de Inmunonutrici\u00f3n y Gen\u00f3mica Nutricional en las Enfermedades Autoinmunes; Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Laboratorio de Inmunolog\u00eda y Biolog\u00eda Celular y Molecular, Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de San Luis Potosi, San Luis Potosi 78210, San Luis Potosi, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Cerpa-Cruz","sequence":"additional","affiliation":[{"name":"Departamento de Reumatolog\u00eda, O.P.D. Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara 44280, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4579-2294","authenticated-orcid":false,"given":"Ulises","family":"De la Cruz-Mosso","sequence":"additional","affiliation":[{"name":"Red de Inmunonutrici\u00f3n y Gen\u00f3mica Nutricional en las Enfermedades Autoinmunes; Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Instituto de Neurociencias Traslacionales, Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid Arthritis","volume":"4","author":"Smolen","year":"2018","journal-title":"Nat. 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