Abstract : Osteoporosis is a common age-related disease with a strong genetic influence. Polymorphisms of ESR1
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Abstract : Osteoporosis is a common age-related disease with a strong genetic influence. Polymorphisms of ESR1 have consistently been shown to be associated with bone mineral density (BMD) and fracture however in regulating bone metabolism ESR1 interacts with both ESR2 and RIZ1. We therefore examined the effects of polymorphisms in the ESR1 ESR2 and RIZ1 genes and their haplotypes on vertebral fractures and BMD in a case-control study comprising 462 osteoporotic patients and 336 controls. In ESR1 we found the variant C allele of the XbaI polymorphism to be associated with decreased risk of vertebral fractures in women (P lt 0.01) whereas in men the T allele seemed protective (P = 0.05). The variant G allele of the PvuII polymorphism decreased the risk of vertebral fractures independently of lumbar spine BMD in women (P = 0.04) but had no effect in men. Haplotype X-P-H (XbaIC PvuIIG and a high number of TA repeats) was associated with decreased risk of vertebral fractures in women (P = 0.04) but not men. In ESR2 the G allele of the AluI polymorphism was associated with increased fracture risk (P = 0.04) and the haplotype that comprises rs1256031T and AluIA increased lumbar spine BMD by 0.04 +/- 0.02 g/cm(2) (P lt 0.05) and decreased the risk of vertebral fractures (P = 0.04). There was no effect of the RIZ1 polymorphism on BMD or fracture risk and no evidence of interaction between the polymorphisms and haplotypes thereof. We confirm that genetic variants in ESR1 and ESR2 but not RIZ1 are important in osteoporosis. We found no evidence of interaction between polymorphisms but we found that the effects of genetic variants in ESR1 might be sex dependent.
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