FRONTAL fibrosing alopecia (FFA) is an increasingly prevalent form of follicular lichen planus, primarily affecting postmenopausal individuals and leading to irreversible hair loss. Previous genome-wide meta-analyses of female FFA have identified risk loci in genes involved in self-antigen presentation and T-cell homeostasis. Additionally, CYP1B1 was shown to have a protective effect against FFA, however, the use of oral contraceptive pills (OCPs) could modulate this effect. The research team, led by Tuntas Rayinda, King’s College London, United Kingdom, sought to investigate whether OCP use modulates the protective effect of the common missense variant in CYP1B1 on FFA risk.
Female patients with FFA were recruited from UK-based dermatology clinics, resulting in the inclusion of 489 women. These patients were matched with unrelated age- and ancestry-matched female controls from the UK Biobank at a 1:66 ratio. Data were collected from July 2015 to September 2017 and analysed from October 2022 to December 2023. The primary outcomes were the modulatory effect of OCP use on the contribution of the CYP1B1 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.
Among 489 female patients with FFA (mean age 65.8 years, 75.7% with OCP history) and 34,254 control individuals (mean age 65.0 years, 91.0% with OCP history), the CYP1B1 risk allele was associated with female FFA in those reporting OCP use (odds ratio [OR]:1.90; 95% confidence interval [CI]: 1.50-2.40; P = 8.41×10−8) but not in those without OCP exposure (OR: 1.16; 95% CI: 0.82-1.64; P =0.39). A full gene-environment interaction model showed a significant additive interaction between c.1358A, p.453Asn, and OCP history on FFA risk (OR: 1.63; 95% CI: 1.07-2.46; P =0.02).
This analysis suggests that the protective effect of the CYP1B1 missense variant on FFA risk may be mediated by OCP exposure. The asparagine-encoding allele at position 453 of CYP1B1 was associated with increased FFA odds only in participants with an OCP history.
Reference
Tuntas R et al. Gene-Environment interaction between CYP1B1 and oral contraception on frontal fibrosing alopecia. JAMA Dermatol. 2024;DOI:10.1001/jamadermatol.2024.1315.
