Gene deletion predicts BMD in postmenopausal women
MedWire News: Deletion of a single gene can have a beneficial effect on bone mineral density (BMD), to the same magnitude as that of hormone replacement therapy (HRT), study findings indicate.
The gene, known as UGT2B17, encodes a glucuronosyltransferase that is the primary androgen-inactivating enzyme. Recently published results from small studies indicate that deletion of UGT2B17 is associated with increased BMD at the hip, increased cortical thickness, and reduced buckling ratio.
Subsequently, the physical boundaries of the UGT2B17 deletion have been described to the nucleotide level, making it practical to design high-throughput polymerase chain reaction assays and analyze gene status in a large number of patients.
Accordingly, Sylvie Giroux (University of Quebec, Canada) and colleagues genotyped 2356 women, of whom 27.8% were found to not express the UGT2B17 gene.
The analysis showed that BMD did not vary by UGT2B17 status in postmenopausal women who had ever used HRT or in premenopausal women.
In contrast, among postmenopausal women who had never used HRT, the presence of one or two UGT2B17 alleles was associated with a significantly lower BMD at the femoral neck (0.842 vs 0.880 g/cm2) and lumbar spine (1.031 vs 1.090 g/cm2) than when both alleles were deleted.
Interestingly, BMD was similar in postmenopausal women who had used HRT and postmenopausal women who had never used HRT and were null allele carriers. Similarly, BMD was similar in pre- and postmenopausal women who had never used HRT and were null carriers.
Age, body weight, and smoking history had no effect on any of the relationships observed.
"In conclusion, we replicated an association observed between UGT2B17 gene deletion and BMD, and we showed that the effect was specific for postmenopausal women who never used HRT," write the authors.
They say that their findings, if validated, support genotyping of UGT2B17 to identify women who would not benefit from taking HRT to improve BMD, and provide a rationale for UGT2B17 as a potential target for novel therapies aimed at preventing bone loss at menopause.
The findings are published in the journal Osteoporosis International.
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Philip Ford