PHACTR3基因与中国汉族和美国高加索人群骨密度的关联研究

研究组前期的全基因组关联研究发现PHACTR3基因与骨折关联，为了检测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PHACTR3基因内及其附近的SNPs与骨密度的关系。首先在中国样本（1627个不相关的汉族样本）和美国样本（2286个不相关高加索样本）中对PHACTR3基因的140个SNPs进行基因分型，然后采用Plink软件检测PHACTR3基因与腰椎和髋部骨密度的关联关系。发现研究组以前报道的与骨折关联的SNPs rs1555364和rs6064822与腰椎和髋部骨密度关联（P=4．89×10^-2-1．26×10^-2）。另外还发现位于PHACTR3基因内含子中3个SNPs位点（rs6027138，rs1182531和rs1182532）与中国人群和白人腰椎骨密度均显著关联，将中国人与白人样本合并起来进行荟萃分析（Meta—analysis），得到合并P值为1．40×10^-3到4．00×10^-4，另外发现rs6064820与髋部BMD相关联，合并P值为6．70×10^-3。本研究进一步证实了PHACTR3基因在骨密度变异中的作用，对骨质疏松发病机制的认识提供了新的理论依据。

Genetic Variants in the PHACTR3 Gene are Associated with Bone Mineral Density in both Chinese and Caucasian Populations

Our previous genome-wide association study detected that PHACTR3 gene was associated with hip fracture.To investigate the relationship between SNPs within and near the PHACTR3 gene and BMD(bone mineral density) at both hip and spine,a fine-mapping association analysis was performed.A total of 140 SNPs were tested in a US Caucasian population(2,286 unrelated subjects) and a Chinese population(1,627 unrelated Han subjects).Plink software was used to test association of PHACTR3 genes with spine and hip bone mineral density.Our study confirmed that two SNPs(rs1555364 and rs6064822)that were previously reported to be associated with hip fracture were also associated with spine and hip BMD,with P values ranging from 4.89×10-2 to 1.26×10-2.Besides the two SNPs,we identified another three SNPs(rs6027138,rs1182531,rs1182532)associated with Chinese and Caucasians spine and hip BMD,with meta-analysis P value ranging from 1.40×10-3 to 4.00×10-4.We also found that rs 6064820 was associated with hip BMD(meta-analysis P=6.70×10-3).This study further highlighted the importance of PHACTR3 gene influencing bone mineral density variation and provided more information for the understanding of the molecular genetic mechanism of osteoporosis.