Kim J, Kim H, Ku S-Y, Suh C S, Kim J H, Kim J G
a Department of Obstetrics and Gynecology, Cha Gangnam Hospital , Cha University , Seoul , Korea ;
b Department of Obstetrics and Gynecology , Seoul National University College of Medicine , Korea ;
Climacteric. 2016;19(1):85-90. doi: 10.3109/13697137.2015.1115476. Epub 2015 Dec 1.
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.
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-κB ligand (sRANKL) and bone turnover markers were measured after 6 months of HT.
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.
The PER1 c.2884C > G polymorphism may be associated with risk of non-response to HT in postmenopausal Korean women.
在本研究中，我们旨在探讨韩国绝经后女性生物钟基因（PER）多态性与激素治疗（HT）后骨反应之间的关联。
对509名接受HT的韩国绝经后女性进行了PER1基因的c.2284C＞G、c.2247C＞T多态性，PER2基因的c.3731G＞A多态性，PER3基因的c.2592G＞A、c.3083T＞C多态性以及PER3基因54bp可变数目串联重复序列（VNTR）的分析。在HT治疗1年后测量腰椎和股骨颈的骨密度（BMD），并在HT治疗6个月后测量血清骨保护素（OPG）、核因子κB受体活化因子配体可溶性受体（sRANKL）水平以及骨转换标志物。
PER1基因的c.2884C＞G多态性和PER3基因54bp VNTR与HT治疗1年后股骨颈BMD的年变化百分比相关（p＜0.05）。PER1基因c.2884C＞G多态性的非CC基因型和PER3基因54bp VNTR的4重复纯合子中股骨颈BMD的变化分别显著低于CC基因型和非4重复纯合子。PER1基因c.2884C＞G多态性与HT治疗无反应（HT治疗后每年BMD丢失＞3%）相关。与CC基因型相比，PER1基因c.2884C＞G多态性的非CC基因型在腰椎和/或股骨颈无反应的风险高1.92倍（p = 0.01）。根据PER1基因c.2884C＞G多态性，HT治疗6个月后骨标志物无显著变化。
PER1基因c.2884C＞G多态性可能与韩国绝经后女性HT治疗无反应的风险相关。
