北京部分汉族男性维生素D受体基因Fok Ⅰ多态性与骨密度的关系

Association between vitamin D receptor genetypes of Fok Ⅰ polymorphism and bone mineral density in male of the Han nationality in Beijing area

背景:骨质疏松症是受遗传和环境因素共同作用的多因子复杂疾病。维生素D受体基因多态性被认为是调控骨量的重要遗传因素,但在不同种族人群中的研究结果仍存在争议。目的:观察维生素D受体基因FokⅠ多态性与北京地区部分汉族男性骨密度的关系,以探求北京地区男性骨质疏松症的遗传易感性。设计、时间及地点:随机对照试验,在2004-09/2007-12在解放军第二炮兵总医院内分泌科和解放军总医院老年病研究所分子生物学实验室共同完成。对象:筛选2004-09/2006-12长期居住北京地区无血缘关系的20～80岁健康汉族男性230人。方法:用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析法检测受试者维生素D受体基因FokⅠ基因型,使用双能X射线吸收测定法检测随机抽取的100例受试者腰椎和髋部的骨密度。主要观察指标:①受试者年龄、身高、体质量。②受试者维生素D受体基因FokⅠ基因型。③受试者L2～4椎体、股骨颈、大转子及Wards三角部位骨密度。结果:受试者维生素D受体基因FokⅠ的基因型及基因频率的分布为FF36.96%,Ff46.96%,ff16.08%,符合Hardy-Weinberg定律;校正年龄、体质量、身高和体质量指数对骨密度的影响后,40～59岁年龄段男性ff基因型组骨密度较FF,Ff基因型低(P=0.037)。其余各年龄段、各部位ff基因型组骨密度大多低于FF,Ff基因型,但差异无显著性意义(P>0.05)。结论:北京地区汉族男性维生素D受体基因FokⅠ多态性分型与骨密度之间可能存在一定关联,该项检测对筛查男性骨质疏松症高危人群的意义需进一步研究。

BACKGROUND： Osteoporosis is a multifactorial disease which is regulated by genetic and environmental factors. Polymorphism of the vitamin D receptor （VDR） gene has been reported to play a major role in variations for genetic regulation of bone mass, but its role within various ethnic populations is controversial. OBJECTIVE： To investigate the association between VDR genetypes of Fok Ⅰ polymorphism and bone mineral density, so as to explore the genetic susceptibility for osteoporosis in male from Beijing. DESIGN, TIME AND SETTING： The randomized controlled observation was performed at Department of Endocrine at the Second Artillery General Hospital of Chinese PLA and Laboratory of Molecular Biology, Institute of Geriatrics and Gerontology, General Hospital of Chinese PLA between September 2004 and December 2007. PARTICIPANTS： A total of 230 healthy male from Han nationality who dwelled in Beijing, aged 20-80 years, were selected from September 2004 to December 2006. METHODS： The genotypes of VDR gene Fok Ⅰ polymorphism were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. Bone mineral density values were determined on random chosen 100 subjects by dual energy X-ray absorptiometry at lumbar vertebra and hip. MAIN OUTCOME MEASURES： （1）Tbe subjects＇ age, height and body weight. （2）The genotypes of VDR gene Fok Ⅰ polymorphism. （3）Bone mineral density values at lumbar spine （L24）, femoral neck, trochanter and Wards triangle. RESULTS： The genetypes and gene frequency distribution of VDR gene Fok Ⅰ polymorphism was FF 36.96%, Ff46.96%, ff 16.08%, in accordance with Hardy-Weinberg equilibrium. After adjusting for age, height, body weight and body mass index, the bone mineral density in the men with ff genetype was lower than with Ff and FF genetypes （P = 0.037）. There was a trend of ff genetype with lower bone mineral density at other sites, but no significant differences in other groups （P 〉 0.05）. CONCLUSION： There is a possible correlation between CDR gene Fok Ⅰ polymorphisms and bone mineral density in Han male of Beijing. It can be employed to screen the high risk population of osteoporosis in men.