{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T23:50:34Z","timestamp":1784418634056,"version":"3.55.0"},"reference-count":15,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Dermatol"],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:sec id=\"ab-dbr240005-4\"><jats:title>Importance<\/jats:title><jats:p>Frontal fibrosing alopecia (FFA) is an increasingly prevalent form of follicular lichen planus, causing irreversible hair loss predominantly in postmenopausal individuals. An earlier genome-wide meta-analysis of female FFA identified risk loci in genes implicated in self-antigen presentation and T-cell homeostasis, including HLA-B*07:02, <jats:italic>ST3GAL1<\/jats:italic>, and <jats:italic>SEMA4B<\/jats:italic>. However, <jats:italic>CYP1B1<\/jats:italic>, which is important for hormone metabolism, was also implicated with the substitution of serine for asparagine at position 453 (c.1358A&amp;amp;gt;G, p.Asn453Ser) exhibiting a protective effect against FFA. Increasing understanding of genetic and environmental variables and their interactions will improve understanding of disease pathogenesis and has the potential to inform risk mitigation strategies.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr240005-5\"><jats:title>Objective<\/jats:title><jats:p>To investigate whether oral contraceptive pill (OCP) use modulates the protective effect of the common missense variant in <jats:italic>CYP1B1<\/jats:italic> (c.1358A&amp;amp;gt;G, p.Asn453Ser) on FFA risk.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr240005-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This gene-environment interaction study using a case-control design enrolled female patients with FFA from UK-based dermatology clinics. The patients were matched with unrelated age- and ancestry-matched female control individuals derived from UK Biobank in a 1:66 ratio, determined by the first 4 principal components from genome-wide genotypes. Data were collected from July 2015 to September 2017, and analyzed from October 2022 to December 2023.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr240005-7\"><jats:title>Main Outcome and Measure<\/jats:title><jats:p>The main outcomes were the modulatory effect of OCP use on the contribution of the <jats:italic>CYP1B1<\/jats:italic> missense variant to female FFA risk and a formal gene-environment interaction test evaluated by a logistic regression model with a multiplicative interaction term, under the assumptions of an additive genetic model interaction term, under the assumptions of an additive genetic model.<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr240005-8\"><jats:title>Results<\/jats:title><jats:p>Of the 489 female patients with FFA, the mean (SD) age was 65.8 (9.7) years, and 370 (75.7%) had a history of OCP use. Of the 34\u202f254 age- and ancestry-matched control individuals, the mean (SD) age was 65.0 (8.4) years, and previous OCP use was reported in 31\u202f177 (91.0%). An association between female FFA and the <jats:italic>CYP1B1<\/jats:italic> risk allele was observed in individuals who reported OCP use (odds ratio, 1.90 [95% CI, 1.50-2.40]; <jats:italic>P<\/jats:italic>\u2009=\u20098.41\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>) but not in those with no documented exposure to OCPs (odds ratio, 1.16 [95% CI, 0.82-1.64]; <jats:italic>P<\/jats:italic>\u2009=\u2009.39). A full gene-environment interaction model demonstrated a significant additive statistical interaction between c.1358A, p.453Asn, and history of OCP use on FFA risk (OR for interaction, 1.63 [95% CI, 1.07-2.46]; P\u2009=\u2009.02)<\/jats:p><\/jats:sec><jats:sec id=\"ab-dbr240005-9\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>This gene-environment interaction analysis suggests that the protective effect of the <jats:italic>CYP1B1<\/jats:italic> missense variant on FFA risk might be mediated by exposure to OCPs. The allele that encodes an asparagine at position 453 of <jats:italic>CYP1B1<\/jats:italic> was associated with increased odds of FFA only in participants with OCP history.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamadermatol.2024.1315","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T15:00:30Z","timestamp":1716994830000},"page":"732","source":"Crossref","is-referenced-by-count":11,"title":["Gene-Environment Interaction Between <i>CYP1B1<\/i> and Oral Contraception on Frontal Fibrosing Alopecia"],"prefix":"10.1001","volume":"160","author":[{"given":"Tuntas","family":"Rayinda","sequence":"first","affiliation":[{"name":"St John\u2019s Institute of Dermatology, King\u2019s College London, London, United Kingdom"},{"name":"Department of Dermatology and Venereology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Sleman, Special Region of Yogyakarta, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila M.","family":"McSweeney","sequence":"additional","affiliation":[{"name":"St John\u2019s Institute of Dermatology, King\u2019s College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Christou","sequence":"additional","affiliation":[{"name":"St John\u2019s Institute of Dermatology, King\u2019s College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuin Ying","family":"Ung","sequence":"additional","affiliation":[{"name":"St John\u2019s Institute of Dermatology, King\u2019s College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Fenton","sequence":"additional","affiliation":[{"name":"St John\u2019s Institute of Dermatology, King\u2019s College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"McGrath","sequence":"additional","affiliation":[{"name":"St John\u2019s Institute of Dermatology, King\u2019s College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Dand","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, King\u2019s College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, King\u2019s College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Tziotzios","sequence":"additional","affiliation":[{"name":"St John\u2019s Institute of Dermatology, King\u2019s College London, London, United 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