Homozygous deletion of the UGT2B17 gene is not associated with osteoporosis risk in elderly Caucasian women

Summary Previously, homozygous deletion of the UGT2B17 gene has shown association with hip fracture. Using a highthroughput qRT-PCR assay, we genotyped UGT2B17 copy number variation (CNV) in 1,347 elderly Caucasian women and examined for effects on bone phenotypes. We found no evidence of association between UGT2B17 CNV and osteoporosis risk in this population. Introduction Genetic studies of osteoporosis commonly examine SNPs in candidate genes or whole genome analyses, but insertions and deletions of DNA, collectively called CNV, also comprise a large amount of the genetic variability between individuals. Previously, homozygous deletion of the UGT2B17 gene in CNV 4q13.2, which encodes an enzyme that mediates the glucuronidation of steroid hormones, has shown association with the risk of hip fracture. Methods We used a quantitative real-time PCR assay for genotyping the UGT2B17 CNV in a well-characterized population study of 1,347 Caucasian women aged 75.2± 2.7 years (mean±SD), to assess the effect of the CNV on bone mass density (BMD) at the total hip site and osteoporosis risk. Results The UGT2B17 CNV distribution was consistent with the expected Hardy–Weinberg distribution and not different from frequencies previously reported in a Caucasian population. Data from ANCOVA of age- and weight-adjusted BMD for UGT2B17 CNV genotype showed no significant difference between genotype groups. Individuals with homozygous or heterozygous deletion of the UGT2B17 gene showed no increased risk of incident fragility fracture. Conclusions These data suggest that quantitative real-time PCR is a rapid and efficient technique for determination of candidate CNVs, including the UGT2B17 CNV; however, we found no evidence of an effect of UGT2B17 CNV on osteoporosis risk in elderly Caucasian women.