ZBTB40基因与中国汉族人群和美国高加索人群骨密度的关联研究  

Genetic Variants in the ZBTB40 Gene are Associated with Bone Mineral Density in Both Chinese and Caucasian Populations

作　　者：谭丽君[1] 杨铁林[2] 刘拥军[3] 邓红文[1,3] 

机构地区：[1]湖南师范大学生命科学学院分子与统计遗传学研究室,中国湖南长沙410081 [2]西安交通大学生命科学与技术学院分子遗传所,中国陕西西安710049 [3]杜兰大学公共卫生和热带医学学院生物信息和基因组学中心

出　　处：《生命科学研究》2012年第4期324-328,共5页Life Science Research

基　　金：国家自然科学基金资助项目(30900810);国家自然科学基金委员会(NSFC)-加拿大卫生研究院(CIHR)健康研究合作计划项目(30811120436);国家自然科学基金委员会和香港研究资助局(RGC)联合基金资助项目(30731160618);NIH(P50 AR055081;R01AG026564;R01 AR050496;RC2 DE020756;R01 AR057049;R03 TW008221);Frankin D.Dickson/Missouri资助项目

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.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.

关 键 词：骨质疏松症 骨密度 ZBTB40基因 关联分析 

分 类 号：R394.3[医药卫生—医学遗传学]