Lorentzon Mattias, Eriksson Anna L, Nilsson Staffan, Mellström Dan, Ohlsson Claes
Center for Bone Research at the Sahlgrenska Academy (CBS), Department of Internal Medicine, Gothenburg University, Gothenburg, Sweden.
J Bone Miner Res. 2007 Aug;22(8):1165-72. doi: 10.1359/jbmr.070416.
In this large population-based study in young men, we show that the COMT val158met polymorphism modulates the association between physical activity, aBMD (DXA), and trabecular vBMD (pQCT).
Peak BMD is an important predictor of future risk of osteoporosis and is largely determined by genetic factors but also by environmental factors, among which physical activity (PA) is a strong contributor. Estrogens are believed to influence the mechanical strain signal generated by bones subjected to mechanical loading. Catechol-O-methyltransferase (COMT) is involved in the degradation of estrogens. A functional polymorphism in the COMT gene (val158met), results in a 60-75% difference in enzyme activity between the val (high activity = H) and met (low activity = L) variants. The aim of this study was to determine if the COMT val158met polymorphism modulates the association between PA and BMD in young men.
The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study consists of 1068 men (age, 18.9 +/- 0.6 yr). Areal BMD (aBMD) was measured by DXA, whereas cortical and trabecular volumetric BMD (vBMD) were measured by pQCT. Study subjects were genotyped and classified as COMT(LL), COMT(HL), or COMT(HH). The amount (h/wk) of PA was determined through questionnaires.
Using a linear regression model (including age, height, weight, smoking, and calcium intake as covariates), significant interactions between the COMT genotype and PA were seen for aBMD at all sites and for trabecular vBMD in both the radius and the tibia. The difference in adjusted aBMD and trabecular vBMD between high (>or=4 h/wk) and low PA (<4 h/wk) was greater in COMT(LL) subjects than in subjects homozygous for the COMT(HH) (total body aBMD: COMT(LL) 4.2% versus COMT(HH) 1.5%, p = 0.02; lumbar spine aBMD: COMT(LL) 7.8% versus COMT(HH) 3.9%, p = 0.04; tibia trabecular vBMD: COMT(LL) 7.1% versus COMT(HH) 1.0%, p < 0.01). The COMT polymorphism was associated with aBMD, at all sites and with trabecular vBMD in the low-PA subjects, but not in their high-PA counterparts.
We show that the COMT val158met polymorphism modulates the association between PA, aBMD, and trabecular vBMD, suggesting that this polymorphism is of importance for BMD in subjects with a low level of PA.
在这项针对年轻男性的大型基于人群的研究中，我们发现儿茶酚-O-甲基转移酶（COMT）基因val158met多态性调节了身体活动、骨密度（DXA测量）和小梁骨体积密度（pQCT测量）之间的关联。
峰值骨密度是未来骨质疏松风险的重要预测指标，很大程度上由遗传因素决定，但也受环境因素影响，其中身体活动（PA）是一个重要因素。雌激素被认为会影响骨骼在承受机械负荷时产生的机械应变信号。儿茶酚-O-甲基转移酶（COMT）参与雌激素的降解。COMT基因的一个功能性多态性（val158met）导致val（高活性 = H）和met（低活性 = L）变体之间酶活性有60 - 75%的差异。本研究的目的是确定COMT val158met多态性是否调节年轻男性中PA与骨密度之间的关联。
哥德堡骨质疏松与肥胖决定因素（GOOD）研究包括1068名男性（年龄，18.9±0.6岁）。采用双能X线吸收法（DXA）测量面积骨密度（aBMD），而皮质骨和小梁骨体积骨密度（vBMD）通过外周定量CT（pQCT）测量。对研究对象进行基因分型，并分为COMT(LL)、COMT(HL)或COMT(HH)。通过问卷确定PA的量（小时/周）。
使用线性回归模型（包括年龄、身高、体重、吸烟和钙摄入量作为协变量），在所有部位的aBMD以及桡骨和胫骨的小梁vBMD方面，观察到COMT基因型与PA之间存在显著交互作用。PA水平高（≥4小时/周）和低（<4小时/周）的COMT(LL)受试者之间调整后的aBMD和小梁vBMD差异大于COMT(HH)纯合子受试者（全身aBMD：COMT(LL)为4.2%，而COMT(HH)为1.5%，p = 0.02；腰椎aBMD：COMT(LL)为7.8%，而COMT(HH)为3.9%，p = 0.04；胫骨小梁vBMD：COMT(LL)为7.1%，而COMT(HH)为1.0%，p < 0.01）。在低PA受试者中，COMT多态性与所有部位的aBMD以及小梁vBMD相关，但在高PA受试者中则不然。
我们发现COMT val158met多态性调节了PA、aBMD和小梁vBMD之间的关联，表明该多态性对PA水平低的受试者的骨密度很重要。
