Yamada Yoshiji, Ando Fujiko, Niino Naoakira, Ohta Shigeo, Shimokata Hiroshi
Department of Gene Therapy, Gifu International Institute of Biotechnology, and Institute of Applied Biochemistry, Mitake, Gifu 505-0116, Japan.
J Mol Med (Berl). 2002 Jul;80(7):452-60. doi: 10.1007/s00109-002-0348-0. Epub 2002 Jun 4.
The estrogen receptor alpha gene is a candidate locus for genetic influence on bone mass. The possible association between two polymorphisms in the first intron of this gene, alone or in combination, and bone mineral density at various sites was examined in participants in the National Institute for Longevity Sciences Longitudinal Study of Aging, a population-based prospective cohort study of aging and age-related diseases. The relationship of the TC ( PvuII) and AG ( XbaI) polymorphisms in the first intron of the estrogen receptor alpha gene to bone mineral density was determined in 2230 subjects (1120 men, 1110 women) and in 2238 subjects (1128 men, 1110 women), respectively, all of whom were community-dwelling individuals aged 40-79 years. Bone mineral density at the radius was measured by peripheral quantitative computed tomography and that for the lumbar spine, right femoral neck, right trochanter, right Ward's triangle, and total body was measured by dual-energy X-ray absorptiometry. Estrogen receptor alpha genotypes were determined with an automated fluorescent allele-specific DNA primer assay system. Analysis of the TC ( PvuII) polymorphism revealed that bone mineral density for the total body, femoral neck, and trochanter was significantly lower in women aged 60 years or over with the CC genotype than in those with the TT genotype, but statistical significance was not achieved after adjustment for age, body mass index, and smoking status. Analysis of the AG ( XbaI) polymorphism revealed that bone mineral density for the femoral neck was significantly lower in women aged 60 years or over with the GG genotype than in those with the AA genotype. After adjustment for age, body mass index, and smoking status, bone mineral density for the femoral neck was significantly lower in women aged 60 years or over with the GG genotype than in those with the AA or AG genotypes. Analysis of combined genotypes in women aged 60 years or over revealed that bone mineral density for the femoral neck was significantly lower in women with the CC/ GG genotype than in those with the TT/ AA or TC/ AA genotypes. After adjustment for age, body mass index, and smoking status, bone mineral density for the femoral neck was significantly lower in women aged 60 years or over with the CC/ GG genotype than in those with other genotypes. No differences in bone mineral density at the various sites were detected among TC ( PvuII), AG ( XbaI), or combined genotypes in women aged under 60 years or in men. These results suggest that the estrogen receptor alpha gene is a susceptibility locus for bone mass, especially for the femoral neck, in elderly Japanese women.
雌激素受体α基因是骨量遗传影响的候选基因座。在国立长寿科学研究所老龄化纵向研究（一项基于人群的老龄化及与年龄相关疾病的前瞻性队列研究）的参与者中，研究了该基因第一个内含子中两个多态性单独或联合与不同部位骨矿物质密度之间的可能关联。分别在2230名受试者（1120名男性，1110名女性）和2238名受试者（1128名男性，1110名女性）中确定雌激素受体α基因第一个内含子中的TC（PvuII）和AG（XbaI）多态性与骨矿物质密度的关系，所有受试者均为年龄在40 - 79岁的社区居住个体。通过外周定量计算机断层扫描测量桡骨的骨矿物质密度，通过双能X线吸收法测量腰椎、右股骨颈、右转子、右沃德三角区和全身的骨矿物质密度。使用自动荧光等位基因特异性DNA引物检测系统确定雌激素受体α基因型。对TC（PvuII）多态性的分析显示，60岁及以上CC基因型女性的全身、股骨颈和转子的骨矿物质密度显著低于TT基因型女性，但在调整年龄、体重指数和吸烟状况后未达到统计学显著性。对AG（XbaI）多态性的分析显示，60岁及以上GG基因型女性的股骨颈骨矿物质密度显著低于AA基因型女性。在调整年龄、体重指数和吸烟状况后，60岁及以上GG基因型女性的股骨颈骨矿物质密度显著低于AA或AG基因型女性。对60岁及以上女性的联合基因型分析显示，CC / GG基因型女性的股骨颈骨矿物质密度显著低于TT / AA或TC / AA基因型女性。在调整年龄、体重指数和吸烟状况后，60岁及以上CC / GG基因型女性的股骨颈骨矿物质密度显著低于其他基因型女性。在60岁以下女性或男性中，未检测到TC（PvuII）、AG（XbaI）或联合基因型在不同部位骨矿物质密度上的差异。这些结果表明，雌激素受体α基因是老年日本女性骨量的易感基因座，尤其是股骨颈。
