CYP3A7*1C polymorphism, serum dehydroepiandrosterone sulphate level and bone mineral density in postmenopausal women
Gábor Speer, Krisztián Bácsi, János P. Kósa & Péter Lakatos
Objective: The CYP3A7 enzyme metabolizes some steroid hormones including dehydroepiandrosterone sulphate (DHEAS). Its expression silenced after birth. Previous study has shown that in case of CYP3A7*1C polymorphism, CYP3A7 enzyme activity persisted a higher level, resulting lower levels of DHEAS in men. The age-related decline of serum DHEAS levels is believed to contribute to osteoporosis. We hypothesized that CYP3A7*1C contribute bone loss through decreased level of serum DHEAS in postmenopausal women.
Patients and methods: 319 postmenopausal women were admitted to study and divided into two subgroups: 217 women with osteoporosis and 102 aged-matched women, without osteoporosis. The CYP3A7*1C polymorphism was genotyped. Serum DHEAS levels and bone mineral density (BMD) were measured.
Results: Homozygous CYP3A7*1C carriers had significantly lower BMD at lumbar spine than that of wild type (T-score with CYP3A7*1C mutant type: −3.27±1.02, T-score with wild type: −1.35±1.53, P=0.041), after a correction of age and DHEAS levels. We did not find significant association between CYP3A7*1C variant and serum DHEAS level in postmenopausal women. Serum DHEAS levels correlated positively with BMD at both lumbar spine (P<0.005) and at femoral neck (P<0.005) in the whole study population.
Conclusion: We have shown the CYP3A7*1C may be associated with decreased bone mass at the lumbar spine independently of serum DHEAS concentrations. This finding and the lack of association between CYP3A7*1C polymorphism and serum DHEAS level in women support the hypothesis that this genetic variation might lead to reduced bone mass through other CYP3A7 hormonal substrates, than DHEAS.