Association of the formiminotransferase N-terminal sub-domain containing gene and thrombospondin, type 1, domain-containing 7A gene with the prevalence of vertebral fracture in 2427 consecutive autopsy cases
Association of the formiminotransferase N-terminal sub-domain containing gene and thrombospondin, type 1, domain-containing 7A gene with the prevalence of vertebral fracture in 2427 consecutive autopsy cases
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含甲亚氨基转移酶 N 末端亚结构域的基因和含血小板反应蛋白 1 型结构域的 7A 基因与 2427 例连续尸检病例中椎体骨折患病率的关系
作者：
Zhou H;Mori S;Kou I;Fuku N;Naka Mieno M;Honma N;Arai T;Sawabe M;Tanaka M;Ikegawa S;Ito H
我们以前报道了2个血小板减少症易感基因--含甲酰亚胺转移酶N-末端亚结构域基因（FONG）和含1型血小板反应蛋白7A结构域基因（THSD 7A）--其中我们发现了两个常见的单核苷酸多态性rs7605378（FONG）和rs 12673692（THSD 7A）。前者与易患骨质疏松症有关，后者与骨密度有关。为了进一步阐明这些多态性在骨质疏松症发病机制中的重要性，我们研究了它们与椎骨骨折发病率的关系。本研究检测了2427例连续日本尸检（1331例男性，平均年龄：79岁; 1096例女性，平均年龄：82岁）肾皮质提取的DNA。通过对临床记录和尸检报告进行全面检查，确定每个受试者一生中是否存在椎骨骨折。经性别和年龄校正后，Logistic回归分析显示，rs7605378（A等位基因）或rs 12673629（A等位基因）的风险等位基因的纯合子具有增加的椎骨骨折的风险。受试者同时为rs7605378的两个风险等位基因纯合，（AA基因型）和rs 12673629（AA基因型）显示椎体骨折的风险显著增高（比值比2.401，95%置信区间1.305-4.416，P= 0.0048）比那些有至少一个rs7605378（AC/CC基因型）或rs 12673629（AG/GG基因型）的非风险等位基因的人。结果表明，日本受试者rs7605378和rs 12673629的风险等位基因纯合子有较高的风险椎骨骨折。
We previously reported 2 osteoporosis-susceptibility genes—formiminotransferase N-terminal sub-domain containing gene (FONG) and thrombospondin, type 1, domain-containing 7A (THSD7A)—in which we identified two common single-nucleotide polymorphisms, rs7605378 (FONG) and rs12673692 (THSD7A). The former was associated with a predisposition to osteoporosis and the latter with bone mineral density. To further elucidate the importance of these polymorphisms in the pathogenesis of osteoporosis, we examined their association with the incidence of vertebral fracture. DNA extracted from the renal cortex of 2427 consecutive Japanese autopsies (1331 men, mean age: 79 years; 1096 women, mean age: 82 years) were examined in this study. The presence or absence of vertebral fracture during each subject’s lifetime was determined by a thorough examination of the clinical records, as well as autopsy reports. After adjustments for sex and age at autopsy, logistic regression analysis revealed that homozygotes for the risk alleles of rs7605378 (A-allele) or rs12673629 (A-allele) possess an increased risk of vertebral fracture. The subjects simultaneously homozygous for both the risk alleles of rs7605378 (AA genotype) and rs12673629 (AA genotype) showed significantly higher risk of vertebral fracture (odds ratio 2.401, 95% confidence interval 1.305–4.416, P= 0.0048) than those who had at least one non-risk allele of either rs7605378 (AC/CC genotypes) or rs12673629 (AG/GG genotypes). The results suggest that Japanese subjects homozygous for the risk alleles of rs7605378 and rs12673629 have a higher risk of vertebral fracture.
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骨质疏松症易感性的遗传决定因素。
DOI：
--
发表时间：
2003
期刊：
Endocrinology and metabolism clinics of North America (Print)
影响因子：
--
作者：
O. Albagha;S. Ralston
通讯作者：
S. Ralston
影响因子：
2.9
作者：
MURLEY, LL;MACKENZIE, RE
通讯作者：
MACKENZIE, RE
真正的遗传与骨矿物质密度的关联。
影响因子：
158.5
作者：
J. Hirschhorn;L. Gennari
通讯作者：
L. Gennari
影响因子：
11.4
作者：
Morimoto, Riyo;Uehara, Shunsuke;Moriyama, Yoshinori
通讯作者：
Moriyama, Yoshinori