Polymorphisms in period genes and bone response to hormone therapy in postmenopausal Korean women

Abstract

Objective In this study, we aimed to explore the association between polymorphisms in the period (PER) gene and bone response to hormone therapy (HT) in postmenopausal Korean women.Methods The PER1 c.2284C>G, c.2247C>T, PER2 c.3731G>A, PER3 c.2592G>A, c.3083T>C polymorphisms, and PER3 54bp variable number of tandem repeats (VNTR) were analyzed in 509 postmenopausal Korean women who received HT. Bone mineral density (BMD) at the lumbar spine and femoral neck before and after 1 year of HT and serum levels of osteoprotegerin (OPG), soluble receptor activator of the nuclear factor-B ligand (sRANKL) and bone turnover markers were measured after 6 months of HT.Results The PER1 c.2884 C>G polymorphism and PER3 54bp VNTR were associated with annual percent changes in BMD of the femoral neck after 1 year of HT (p<0.05). Changes in BMD at the femoral neck in the non-CC genotype of the PER1 c.2884C>G polymorphism and in the 4-repeat homozygote of PER3 54bp VNTR were significantly lower than those in CC genotype and non-4-repeat homozygote, respectively. The PER1 c.2884C>G polymorphism was associated with the non-response (>3% BMD loss/year after HT) of HT. The non-CC genotype of the PER1 c.2884C>G polymorphism showed a 1.92-times higher risk of non-response at the lumbar spine and/or femoral neck (p=0.01) compared with the CC genotype. No significant changes in bone markers after 6 months of HT were noted according to the PER1 c.2884C>G polymorphism.Conclusions The PER1 c.2884C>G polymorphism may be associated with risk of non-response to HT in postmenopausal Korean women.