Mitochondria-wide association study of common variants in osteoporosis.
Mitochondria-wide association study of common variants in osteoporosis.
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DOI：
10.1111/j.1469-1809.2011.00663.x
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发表时间：
2011-09
影响因子：
1.9
通讯作者：
Deng HW
中科院分区：
文献类型：
--
作者：
Guo Y;Yang TL;Liu YZ;Shen H;Lei SF;Yu N;Chen J;Xu T;Cheng Y;Tian Q;Yu P;Deng HW
许多证据表明，线粒体DNA（mtDNA）变异参与了人类复杂疾病的发病机制，特别是与年龄相关的疾病。骨质疏松症是一种典型的与年龄相关的复杂疾病。然而，线粒体DNA变异在骨质疏松症易感性中的作用在很大程度上是未知的。在这项研究中，我们在高加索人中进行了骨质疏松症的全脑关联研究。使用Affytelium全基因组SNP阵列6.0对2，286名无关高加索受试者的大样本中的445个线粒体单核苷酸多态性（mtSNPs）进行基因分型，72个mtSNPs在质量控制中存活。我们首先检测了单个mtSNP与骨密度（BMD）之间的关联，并确定NADH脱氢酶2基因（ND 2）内的mtSNP，mt4823 C/A多态性与髋部BMD密切相关（P = 2.05 × 10−4），即使在保守的Bonferroni校正后，mt4823的C等位基因也与髋部BMD降低相关，估计效应量（β）为~ 0.044.发现细胞色素B基因（CytB）中的另一个SNP mt 15885与脊柱（P = 1.66×10−3）和髋部BMD（P = 0.023）相关。mt 15885的T等位基因对脊柱骨密度（β = 0.064）和髋部骨密度（β = 0.038）有保护作用。接下来，我们将受试者分为9个常见的欧洲单倍型群，并进行关联分析。被归类为单倍群X的受试者的平均髋部BMD值显著低于其他受试者（P = 0.040）。我们的研究结果强调了mtDNA变异在影响BMD变异和骨质疏松风险方面的重要性。
Many lines of evidence suggest that mitochondrial DNA (mtDNA) variants are involved in the pathogenesis of human complex diseases, especially for age-related disorders. Osteoporosis is a typical age-related complex disease. However, the role of mtDNA variants in the susceptibility of osteoporosis is largely unknown. In this study, we performed a mitochondria-wide association study for osteoporosis in Caucasians. A total of 445 mitochondrial single nucleotide polymorphisms (mtSNPs) were genotyped in a large sample of 2,286 unrelated Caucasian subjects by using the Affymetrix Genome-Wide SNP Array 6.0, and 72 mtSNPs survived the quality control. We first tested for association between single-mtSNP and bone mineral density (BMD), and identified that, a mtSNP within the NADH dehydrogenase 2 gene (ND2), mt4823 C/A polymorphism, was strongly associated with hip BMD (P = 2.05 × 10−4), even after conservative Bonferroni correction‥ The C allele of mt4823 was associated with reduced hip BMD and the effect size (β) was estimated to be ~0.044. Another SNP mt15885 within the Cytochrome b gene (Cytb) was found to be associated both with spine (P = 1.66×10−3) and hip BMD (P = 0.023). The T allele of mt15885 had a protective effect on spine (β = 0.064) and hip BMD (β = 0.038). Next, we classified subjects into the nine common European haplogroups and conducted association analyses. Subjects classified as haplogroup X had significantly lower mean hip BMD values than others (P = 0.040). Our results highlighted the importance of mtDNA variants in influencing BMD variation and risk to osteoporosis.
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DOI：
10.1038/nrg1606
发表时间：
2005-05
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.1
作者：
Deng, HW;Mahaney, MC;Recker, RR
通讯作者：
Recker, RR
影响因子：
9.8
作者：
Macaulay, V;Richards, M;Torroni, A
通讯作者：
Torroni, A
影响因子：
9.8
作者：
van der Walt, JM;Nicodemus, KK;Vance, JM
通讯作者：
Vance, JM
影响因子：
11.2
作者：
Pyle, A;Foltynie, T;Chinnery, PF
通讯作者：
Chinnery, PF