Mutations in the LRP4 and LRP5 genes are associated with bone mineral density in Maltese postmenopausal women

Abstract

BACKGROUND: Osteoporosis is a multifactorial skeletal disease characterised by low bone mass leading to increased fracture risk. Members of the low-density lipoprotein receptor-related protein (LRP) gene family play a role in osteoblastogenesis

through the Wingless (Wnt)/Beta-catenin pathway. LRP4 con- trols the actions of sclerostin, a Wnt inhibitor, whereas LRP5

promotes bone formation. The aim was to evaluate the effect of four non-synonymous coding polymorphisms in relation to

bone mineral density (BMD) and low-trauma fractures in Mal- tese postmenopausal women. Genotyped variants were the

LRP4 rs2306033 (C>T) and rs6485702 (G>A) variants, and the LRP5 rs4988321 (G>A) and rs3736228 (C>T) variants.

METHODS: Research subjects were 1045 women aged 40 to 79 years, subdivided in three BMD groups without a fracture history: normal, osteopenic or osteoporotic. Women with a fracture history were classified as cases. Genotyping was

performed by polymerase chain reaction and restriction frag- ment length polymorphism, or by real-time PCR. Odds ratios

were computed using logistic regression analysis adjusted for age and clinical risk factors.

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