Bone Mineral Density Quantitative Trait Locus 12

A number sign (#) is used with this entry because of evidence that variation in bone mineral density (BMD) is associated with copy number variation of the UGT2B17 gene (601903).

For a discussion of genetic heterogeneity of bone mineral density (BMD), see BMND1 (601884).

Mapping

Yang et al. (2008) performed a case-control genomewide analysis of copy number variation (CNV) in 350 elderly Chinese individuals with osteoporosis-related hip fracture and 350 geography- and age-matched controls and found CNV on chromosome 4q13.2 to be strongly associated with osteoporotic fracture (p = 2.0 x 10(-4), corrected p = 0.02; odds ratio = 1.73).

Molecular Genetics

Using PCR and electrophoresis as well as real-time PCR in 60 Chinese individuals, 20 for each copy-number genotype predicted by the Affymetrix copy number analysis tool (CNAT), Yang et al. (2008) identified a 150-kb deletion on chromosome 4q13.2 encompassing the entire UGT2B17 gene (601903.0001). The authors replicated the association between UGT2B17 CNV and osteoporotic fracture in an independent Chinese sample of 399 patients with osteoporosis-related hip fracture and 400 age-matched controls (p = 6.34 x 10(-3)), and demonstrated an increased risk of osteoporotic fracture in individuals with an existing UGT2B17 gene (odds ratio = 1.58; p = 0.01). Yang et al. (2008) also found consistently significant association between UGT2B17 CNV and major risk factors for osteoporotic fracture in an independent sample of 689 Chinese and 1,000 Caucasian individuals. Because UBT2B17 encodes an enzyme that catabolizes steroid hormones, the authors measured serum testosterone and estradiol levels in an independent sample of 236 young Chinese males and found that those without UGT2B17 had significantly higher concentrations of testosterone and estradiol. Yang et al. (2008) concluded that UGT2B17 CNV plays an important role in the pathogenesis of osteoporosis.