中文摘要：

最近的全基因组关联研究发现ZBTB40（zinc finger and BTB domain containing 40）基因是一个潜在的调节骨密度的新基因,为了可靠地验证该基因与骨密度的关联关系,采用精细定位关联研究来检测ZBTB40基因内及其附近的SNPs与骨密度的关系.首先在中国样本（1 627个不相关的汉族样本）和美国样本（2 286个不相关高加索样本）中对ZBTB40基因的50个SNPs进行基因分型,然后采用Plink软件检测ZBTB40基因与腰椎和髋部骨密度的关联关系.证实了以前报道的SNPs rs7524102与腰椎和髋部骨密度的关联关系.另外还发现5个SNPs（rs10917209、rs6426748、rs4433361、rs3856183和rs7550872）与腰椎和髋部骨密度相关联.其中最显著的SNP是位于ZBTB40基因上游区域的rs6426748,其与腰椎骨密度的关联P值为9.82×10-4,多重检验校正后仍然显著.连锁不平衡分析表明rs6426748与rs10917209,rs7524102和rs7550872呈现高度连锁关系,位于长度为27 kb的单体型块内,因此ZBTB40基因的功能致病位点可能是rs6426748或该单体型块内某一未分型的SNP.

英文摘要：

Recent genome-wide association study detected ZBTB40（zinc finger and BTB domain containing 40） gene as a new osteoporosis susceptibility gene.To investigate the relationship between SNPs within and near the ZBTB40 gene and BMD（bone mineral density） at both hip and spine,a fine-mapping association analysis was performed.A total of 50 SNPs were tested in a US Caucasian population（2 286 unrelated sub-jects） and a Chinese population（1 627 unrelated Han subjects）.Plink software was used to test the associa-tion of ZBTB40 gene with spine and hip bone mineral density.Our study confirmed the previous report that the SNPs rs7524102 was associated with spine and hip BMD.Besides the two SNPs,we identified another five SNPs（rs10917209,rs6426748,rs4433361,rs3856183 and rs7550872） associated with spine and hip BMD.The most significant SNP was rs6426748 located in the upstream of ZBTB40 gene with P value of9.82×10-4,which remained significant after multiple test correction.rs6426748 was in high linkage disequi-librium with rs10917209,rs7524102 and rs7550872,which located in a 27 kb haplotype block,therefore the functional variant of ZBTB40 gene possibly was rs6426748 or other un-genotyped SNP located in these hap-lotype block.