CYP1A1 Variant Linked to Weight Gain During Long-Term Glucocorticoid Use

Long-term glucocorticoid treatment can cause adverse effects, including weight gain and bone loss; genetic variation may contribute to differences between patients. This observational study assessed 70 adults taking at least 5 mg/day of glucocorticoids for more than three months. Clinical and bone-health measures were collected at baseline and five-year follow-up, and CYP1A1 variants were identified by gene sequencing.

Nine participants carried the rs1799814 variant. Compared with other participants, they had a higher BMI (29.3 vs 25.5; p=0.019) and a greater five-year BMI increase (1.7 vs −0.32; p=0.02), adjusted for cumulative glucocorticoid dose. They also had lower NTx levels (21 vs 40 nmol/mmol; p=0.003); differences in CTx and osteocalcin were not statistically significant. No association was found between CYP1A1 variants and osteoporosis or fractures, BMD, or TBS.

The findings suggest a possible association between rs1799814 and selected glucocorticoid-related effects, but do not establish reduced glucocorticoid metabolism as the cause. The small number of variant carriers and absence of associations with bone outcomes limit clinical interpretation; the study does not support using CYP1A1 testing to guide treatment.