Gene-Environment Interaction Between CYP1B1 and Oral Contraception on Frontal Fibrosing Alopecia

Area of Science:

• Genetics
• Dermatology
• Pharmacogenomics

Background:

• Frontal fibrosing alopecia (FFA) is an increasingly common form of scarring alopecia, primarily affecting postmenopausal women.
• Genetic studies have identified risk loci, including a protective variant in the CYP1B1 gene (c.1358A>G, p.Asn453Ser) involved in hormone metabolism.

Purpose of the Study:

• To investigate if oral contraceptive pill (OCP) use modifies the protective association of the CYP1B1 p.Asn453Ser variant with FFA risk.
• To explore gene-environment interactions in the pathogenesis of frontal fibrosing alopecia.

Main Methods:

• A case-control study design was employed, enrolling female FFA patients and age/ancestry-matched controls from the UK Biobank.
• Genome-wide genotypes were used for matching, and logistic regression models tested for gene-environment interaction between OCP use and the CYP1B1 variant.

Main Results:

• The protective effect of the CYP1B1 p.Asn453Ser variant was observed only in women with a history of OCP use (OR, 1.90).
• No significant association was found in women without OCP exposure (OR, 1.16).
• A significant additive statistical interaction was detected between the CYP1B1 variant and OCP use (P = .02).

Conclusions:

• The findings suggest that oral contraceptive pill use may mediate or mask the protective effect of the CYP1B1 p.Asn453Ser variant on frontal fibrosing alopecia risk.
• This highlights a critical gene-environment interaction influencing susceptibility to FFA.