Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women.
Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women.
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DOI：
10.1038/ejhg.2011.245
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发表时间：
2012-05
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影响因子：
--
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中科院分区：
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P2 X7受体基因（P2 RX 7）具有高度多态性，具有五种先前描述的功能丧失（LOF）单核苷酸多态性（SNP; c.151+1G>T，c.946G>A，c.1096C>G，c.1513A>C和c.1729T>A）和一种功能获得SNP（c.489C>T）。本研究的目的是确定功能性P2 RX 7 SNPs是否与绝经后妇女腰椎（LS）骨矿物质密度（BMD）相关，BMD是椎骨骨折风险的关键决定因素。我们对来自阿伯丁前瞻性骨质疏松筛查研究（APOSS）的506名绝经后妇女进行了上述SNP的基因分型。在基线和6-7年随访时测量腰椎BMD。P2 RX 7基因分型通过均质延伸进行。我们发现c.946A（p.Arg307Gln）与基线（P=0.004，β=-0.12）和随访（P=0.002，β=-0.13）时LS-BMD较低相关。进一步的分析显示，LOF SNP的受试者（n=48）的LS-BMD年变化百分比比6个SNP位点的野生型受试者高近9倍（n=84;损失率分别为-0.94%/年和-0.11%/年，P=0.0005，非配对t检验）。这是第一份描述c.946A（p.Arg307Gln）LOF SNP与低LS-BMD相关的报告，其他导致P2 X7受体功能降低或无功能的LOF SNP可能导致骨丢失加速。P2 RX 7的某些多态性变体可以识别患骨质疏松症风险更大的女性。
The P2X7 receptor gene (P2RX7) is highly polymorphic with five previously described loss-of-function (LOF) single-nucleotide polymorphisms (SNP; c.151+1G>T, c.946G>A, c.1096C>G, c.1513A>C and c.1729T>A) and one gain-of-function SNP (c.489C>T). The purpose of this study was to determine whether the functional P2RX7 SNPs are associated with lumbar spine (LS) bone mineral density (BMD), a key determinant of vertebral fracture risk, in post-menopausal women. We genotyped 506 post-menopausal women from the Aberdeen Prospective Osteoporosis Screening Study (APOSS) for the above SNPs. Lumbar spine BMD was measured at baseline and at 6–7 year follow-up. P2RX7 genotyping was performed by homogeneous mass extension. We found association of c.946A (p.Arg307Gln) with lower LS-BMD at baseline (P=0.004, β=−0.12) and follow-up (P=0.002, β=−0.13). Further analysis showed that a combined group of subjects who had LOF SNPs (n=48) had nearly ninefold greater annualised percent change in LS-BMD than subjects who were wild type at the six SNP positions (n=84; rate of loss=−0.94%/year and −0.11%/year, respectively, P=0.0005, unpaired t-test). This is the first report that describes association of the c.946A (p.Arg307Gln) LOF SNP with low LS-BMD, and that other LOF SNPs, which result in reduced or no function of the P2X7 receptor, may contribute to accelerated bone loss. Certain polymorphic variants of P2RX7 may identify women at greater risk of developing osteoporosis.
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影响因子：
4.8
作者：
Jorgensen, NR;Henriksen, Z;Steinberg, TH
通讯作者：
Steinberg, TH
影响因子：
5.5
作者：
Humphreys, BD;Dubyak, GR
通讯作者：
Dubyak, GR
影响因子：
6.2
作者：
MacDonald, HM;McGuigan, FA;Reid, DM
通讯作者：
Reid, DM
DOI：
10.1615/critreveukaryotgeneexpr.v13.i24.150
发表时间：
2003-01-01
影响因子：
1.6
作者：
Gartland, A;Buckley, KA;Gallagher, JA
通讯作者：
Gallagher, JA
影响因子：
6.2
作者：
Gartland, A;Hipskind, RA;Bowler, WB
通讯作者：
Bowler, WB