The role of estrogen receptor-α gene TA polymorphism and aromatase gene TTTA polymorphism on peak bone mass attainment in males: is there an additive negative effect of certain allele combinations?
The role of estrogen receptor-α gene TA polymorphism and aromatase gene TTTA polymorphism on peak bone mass attainment in males: is there an additive negative effect of certain allele combinations?
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DOI：
10.1007/s00774-008-0029-3
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发表时间：
2009-03-01
影响因子：
3.3
通讯作者：
Korsic, Mirko
中科院分区：
文献类型：
--
作者：
Kastelan, Darko;Grubic, Zorana;Korsic, Mirko
男性特发性骨质疏松症主要受到低峰值骨量的影响，这是强遗传控制下的一个特征。在许多候选基因中，由于雌激素在骨质疏松症病理生理学中的重要作用，α-雌激素受体（ERα）和CYP19基因特别令人感兴趣。在本研究中，我们检查了 ER α 基因胸腺嘧啶腺嘌呤 (TA) 多态性和芳香酶基因 TTTA 多态性的某些等位基因组合与年轻男性骨矿物质密度 (BMD) 的关联。研究样本由 92 名年龄在 21-35 岁之间的无关健康男性志愿者组成。测量每个受试者的腰椎和股骨近端 BMD、骨转换参数和 25-OHD 水平。两个 ER α (TA) (n) 等位基因（等位基因 19 和等位基因 21）被发现与较低的 BMD 相关。等位基因 19 的存在与显着较低的腰椎 (P = 0.006) 和转子 (P = 0.02) BMD 相关，而等位基因 21 阳性的受试者具有显着较低的腰椎 (P = 0.04)、转子 (P = 0.02) 和全髋 (P = 0.03) BMD。具有 CYP19 (TTTA)(7-3)/ER α (TA)(19) 等位基因组合的男性腰椎 BMD 显着较低 (P = 0.02)，而具有 CYP19 (TTTA)(7-3)/ER α (TA)(21) 等位基因组合的男性在所有三个测量值中的 BMD 均显着较低，即腰椎 (P = 0.02)、股骨颈 (P = 0.02) 0.02）和总髋关节（P = 0.008）。这些高风险等位基因的特定组合与单独的任何一个等位基因相比，与较低的中位腰椎、股骨颈和总髋部 BMD 相关，表明两个风险等位基因对峰值骨量的负面影响相加。
Idiopathic osteoporosis in males is influenced predominantly by low peak bone mass as a feature under a strong genetic control. Among a number of candidate genes, alpha-estrogen receptor (ER alpha) and CYP19 genes are of particular interest due to important role of estrogen in pathophysiology of osteoporosis. In the present study we examined the association of certain allelic combinations of ER alpha gene thymine-adenine (TA) polymorphism and aromatase gene TTTA polymorphism on bone mineral density (BMD) in young men. The study sample consisted of 92 unrelated healthy male volunteers, aged 21-35. In each subject, lumbar spine and proximal femur BMD, parameters of bone turnover and 25-OHD level were measured. Two ER alpha (TA) (n) alleles, allele 19 and allele 21, were found to be associated with lower BMD. The presence of allele 19 was associated with significantly lower lumbar spine (P = 0.006) and trochanter (P = 0.02) BMD while the subjects positive for allele 21 had significantly lower lumbar spine (P = 0.04), trochanter (P = 0.02) and total hip (P = 0.03) BMD. Men with CYP19 (TTTA)(7-3)/ER alpha (TA)(19) allele combination had significantly lower lumbar spine BMD (P = 0.02) and those with CYP19 (TTTA)(7-3)/ER alpha (TA)(21) allele combination had significantly lower BMD for all three measurements, i.e. lumbar spine (P = 0.02), femoral neck (P = 0.02) and total hip (P = 0.008). These particular combinations of high-risk alleles were associated with lower median lumbar spine, femoral neck and total hip BMD than either of the allele alone suggesting that negative effect of two risk alleles on peak bone mass add up.