Linkage of osteoporosis to chromosome 20p12 and association to BMP2.
Linkage of osteoporosis to chromosome 20p12 and association to BMP2.
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DOI：
10.1371/journal.pbio.0000069
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发表时间：
2003-12
期刊：
影响因子：
9.8
通讯作者：
Stefansson K
中科院分区：
文献类型：
--
作者：
Styrkarsdottir U;Cazier JB;Kong A;Rolfsson O;Larsen H;Bjarnadottir E;Johannsdottir VD;Sigurdardottir MS;Bagger Y;Christiansen C;Reynisdottir I;Grant SF;Jonasson K;Frigge ML;Gulcher JR;Sigurdsson G;Stefansson K
骨质疏松性骨折是老年人群发病和死亡的主要原因。骨质疏松症被定义为低骨矿物质密度 (BMD) 和相关骨折，其重要的遗传成分目前尚不清楚。使用结合骨质疏松性骨折和 BMD 测量的表型对冰岛大量骨质疏松症大家族进行连锁分析，显示与染色体 20p12.3 的连锁（多点等位基因共享 LOD，5.10；p 值，6.3 × 10−7），在调整测试的表型数量和全基因组搜索后，结果具有统计显着性。使用紧密间隔的多态性标记进行后续关联分析。骨形态发生蛋白 2 (BMP2) 基因中的三种变异、一种错义多态性和两种匿名单核苷酸多态性单倍型，被确定与冰岛患者的骨质疏松症相关。这种关联与骨质疏松表型的许多定义有关，包括绝经前后的骨质疏松性骨折以及低骨密度。对丹麦绝经后妇女队列进行了一项复制研究，以证实这三个已识别变异的贡献。总之，我们发现 20 号染色体短臂上的一个区域包含一个或多个似乎是骨质疏松症和骨质疏松性骨折主要危险因素的基因，并且我们的证据支持 BMP2 至少是这些基因之一的观点。对冰岛家庭的遗传分析和对丹麦人群的重复研究提供了证据，表明 BMP2 基因的变异可能导致骨质疏松症
Osteoporotic fractures are a major cause of morbidity and mortality in ageing populations. Osteoporosis, defined as low bone mineral density (BMD) and associated fractures, have significant genetic components that are largely unknown. Linkage analysis in a large number of extended osteoporosis families in Iceland, using a phenotype that combines osteoporotic fractures and BMD measurements, showed linkage to Chromosome 20p12.3 (multipoint allele-sharing LOD, 5.10; p value, 6.3 × 10−7), results that are statistically significant after adjusting for the number of phenotypes tested and the genome-wide search. A follow-up association analysis using closely spaced polymorphic markers was performed. Three variants in the bone morphogenetic protein 2 (BMP2) gene, a missense polymorphism and two anonymous single nucleotide polymorphism haplotypes, were determined to be associated with osteoporosis in the Icelandic patients. The association is seen with many definitions of an osteoporotic phenotype, including osteoporotic fractures as well as low BMD, both before and after menopause. A replication study with a Danish cohort of postmenopausal women was conducted to confirm the contribution of the three identified variants. In conclusion, we find that a region on the short arm of Chromosome 20 contains a gene or genes that appear to be a major risk factor for osteoporosis and osteoporotic fractures, and our evidence supports the view that BMP2 is at least one of these genes. Genetic analysis of Icelandic families and a replication study in a Danish population provide evidence that variation in the gene BMP2 might contribute to osteoporosis
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30.8
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