CNR2基因多态性与汉族绝经女性骨质疏松症的遗传关联研究

The associations of common variants in CNR2 gene with bone mineral density and osteoporosis in Han Chinese postmenopausal women

目的探讨中国汉族绝经后女性群体中CNR2基因与骨密度(BMD)和骨质疏松症易感性的关联性。方法共选取骨质疏松症样本1032例,健康对照样本2089例。分析了3121例中国汉族绝经后女性样本CNR2基因区域的39个SNP位点与BMD和骨质疏松的关联性。结果通过对3121例样本的分析,发现rs4237和rs2501431与骨密度及骨质疏松症的发病显著相关(P=0.020、0.017),并且rs2501431TT基因型和rs4237AA基因型携带者相比于其他基因型的绝经后女性具有较低的腰椎和股骨颈骨密度。此外,单倍型分析结果提示分别包含CNR2基因中的rs4237和rs2501431在内的两个单倍型区段与骨密度及骨质疏松症发病具有显著相关(P均<0.001),并且在rs3003336-rs2501431-rs2502992-rs250143单倍型区段的ATTT单倍型是风险单倍型,且在疾病组出现的频率是对照组的4倍以上。结论研究结果进一步揭示CNR2基因在骨质疏松发病机制中的重要作用,CNR2基因可能是汉族绝经后女性群体中骨密度降低和骨质疏松症发生的重要遗传风险因素。

Objective To investigate whether CNR2 gene,which has been shown to be related to osteoporosis in some populations,is associated with bone mineral density（ BMD） or osteoporosis in Han Chinese postmenopausal women. Methods We examine 39 SNPs covering the region of CNR2 gene in 3121 Han Chinese postmenopausal women,consisting of 1032 osteoporosis patients and 2089 healthy controls,and evaluated their association with BMD and osteoporosis. Results We found that rs4237 and rs2501431 were significantly associated with BMD and osteoporosis（ corrected P = 0. 020 and 0. 017） in our sample,and the TT genotype of rs2501431 and the AA genotype of rs4237 had lower lumbar spine and femoral neck BMD compared with other genotypes. Additionally,analyses by haplotypes indicated that two haplotype blocks,containing rs4237 and rs2501431 respectively,in the CNR2 gene significantly associated with BMD and osteoporosis（ both global permutation P〈0. 001）,and a risk haplotype（ ATTT） in the block of rs3003336-rs2501431-rs2502992-rs2501432 had an almost 4-fold increase in the osteoporosis cases. Conclusion Our results provide further supportive evidence for an important role of CNR2 gene in the etiology of osteoporosis and suggest that it may be a genetic risk factor for BMD and osteoporosis in Han Chinese postmenopausal women.