CAJ | 학술논문

峰值骨密度是由遗传和环境因素及其相互作用共同决定的复杂性状.维生素D受体基因、雌激素α受体基因、白介素6基因、副甲状腺素基因、Ⅰ型胶原α2基因、骨钙素基因、α2巯基糖蛋白基因是与骨代谢相关的7个重要的候选基因.本研究旨在检测这7个候选基因之间的相互作用对中国女性峰值骨密度的影响.样本为中国上海的361个无关、健康的绝经前女性,均为汉族人,年龄为20～44岁.采用Hologic QDR 2000+双能X射线扫描仪对腰椎与髋部的骨密度进行了检测.采用聚合酶链式反应-限制性片段长度多态分析方法对每个个体的以下8个多态性标记位点进行基因分型:维生素D受体基因的Apa Ⅰ位点,雌激素α受体基因的PvuⅡ和Xba Ⅰ位点,白介素6基因的BsrB Ⅰ位点,副甲状腺素基因的BstB Ⅰ位点,Ⅰ型胶原α2基因的Msp Ⅰ位点,骨钙素基因的HindⅢ位点,α2巯基糖蛋白基因的Sac Ⅰ位点.采用二元方差分析对基因相互作用与骨密度的关系进行研究.结果表明,白介素基因和雌激素α受体基因(PvuⅡ)的相互作用对髋部(P=0.019)、转子间区(P=0.016)和股骨颈(P=0.019)的骨密度有显著作用.在这3个部位,GGPp基因型携带者比GGPP基因型携带者的骨密度值分别高出18.0%、19.5%和14.8%.另外观察到α2巯基糖蛋白基因与白介素6基因的相互作用对股骨颈骨密度有显著影响(P=0.046).GGSS基因型携带者的股骨颈骨密度值比GGSs基因型携带者高出18.8%.该项群体水平的统计分析表明:对于中国女性峰值骨密度的遗传决定,白介素基因和雌激素α受体基因、α2巯基糖蛋白基因的相互作用显著.
봉치골밀도시유유전화배경인소급기상호작용공동결정적복잡성상.유생소D수체기인、자격소α수체기인、백개소6기인、부갑상선소기인、Ⅰ형효원α2기인、골개소기인、α2구기당단백기인시여골대사상관적7개중요적후선기인.본연구지재검측저7개후선기인지간적상호작용대중국녀성봉치골밀도적영향.양본위중국상해적361개무관、건강적절경전녀성,균위한족인,년령위20～44세.채용Hologic QDR 2000+쌍능X사선소묘의대요추여관부적골밀도진행료검측.채용취합매련식반응-한제성편단장도다태분석방법대매개개체적이하8개다태성표기위점진행기인분형:유생소D수체기인적Apa Ⅰ위점,자격소α수체기인적PvuⅡ화Xba Ⅰ위점,백개소6기인적BsrB Ⅰ위점,부갑상선소기인적BstB Ⅰ위점,Ⅰ형효원α2기인적Msp Ⅰ위점,골개소기인적HindⅢ위점,α2구기당단백기인적Sac Ⅰ위점.채용이원방차분석대기인상호작용여골밀도적관계진행연구.결과표명,백개소기인화자격소α수체기인(PvuⅡ)적상호작용대관부(P=0.019)、전자간구(P=0.016)화고골경(P=0.019)적골밀도유현저작용.재저3개부위,GGPp기인형휴대자비GGPP기인형휴대자적골밀도치분별고출18.0%、19.5%화14.8%.령외관찰도α2구기당단백기인여백개소6기인적상호작용대고골경골밀도유현저영향(P=0.046).GGSS기인형휴대자적고골경골밀도치비GGSs기인형휴대자고출18.8%.해항군체수평적통계분석표명:대우중국녀성봉치골밀도적유전결정,백개소기인화자격소α수체기인、α2구기당단백기인적상호작용현저.
Peak bone mass (PBM) is a complex trait,determined by both genetic and environmental factors and also their interactions. Vitamin D receptor ( VDR), estrogen receptor α ( ERα), interleukin 6 ( IL6), parathyroid hormone (PTH) ,collagen type Ⅰ alpha 2 ( COL1A2), bone Gla protein ( BGP), alpha2-HS glycoprotein (AHSG) are among the important candidate genes of bone metabolism. The study aims to detect significant effect of potential inter-genic action underlying PBM in Chinese females. 361 unrelated healthy premenopausal Chinese females (aged 20 -44 years) with Han ethnicity were recruited from the Shanghai city in China. Bone mineral density (BMD) at the hip and the lumbar spine (L1-4) was measured using a Hologic QDR 2000 + dual-energy X-ray absorptiometry (DXA) scanner. Eight polymorphisms among the seven genes were genotyped,i. e. Apa Ⅰ in VDR, Pvu Ⅱ and Xba Ⅰ in ERα ( ERX and ERP, respectively), BsrB Ⅰ in IL6, BstB Ⅰ in PTH, Msp Ⅰ in COL1A2,Hind Ⅲ in BGP, and Sac l in AHSG, using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) methods. Two-way analysis of variance (ANOVA) showed significant effects of IL6 × ERP interaction on PBM at the total hip (P=0.019) ,intertrochanter ( P =0.016) ,and femoral neck ( P =0. 019). The BMD difference between GGPp carriers and GGpp subjects (at these two loci) amounted to 18.0% ,19.5% ,and 14.8% at the hip,intertrochanter,and femoral neck,respectively. The potential interaction effect of AHSG × IL6 was observed on femoral neck PBM ( P=0. 046). GGSS individuals (at these two loci)had, on average, 18.8 % higher femoral neck BM D than those subjects with GGSs genotype. The population-level statistical analysis indicates that IL6 × ERP and AHSG × IL6 have significant inter-genic effect on the genetic determination of PBM in Chinese females.