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| 4q22.1区域SNP对汉族绝经后妇女骨密度及骨质疏松易感性的作用 |
| 4q22.1 contributes to bone mineral density and osteoporosis susceptibility in postmenopausal women of Han population |
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| DOI：10.3969/j.issn.1006-7108.2015.10.012 |
| 中文关键词: 绝经后骨质疏松症 骨密度 单核苷酸多态性 单倍型 MassARRAY 基因分型 关联分析 |
| 英文关键词:Postmenopausal osteoporosis Bone mineral density SNP Haplotype Mass ARRAY genotyping Association analysis |
| 基金项目:陕西省自然科学基础研究计划（2015JM8422）；中国博士后科学基金资助项目(M532029)；中央高校基本科研业务费专项资金(08142024,08143003) |
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| 中文摘要: |
| 目的 探讨4q22.1区域易感基因或易感区域的遗传多态性在汉族绝经后女性骨质疏松群体中是否与骨密度和骨质疏松症易感性相关联。方法 使用HaploView搜索国际单体型图谱计划（International HapMap Project，HapMap）数据库位于rs6532023上游20 kb到下游20 kb区域的所有SNP，选择其中在中国北京汉族群体中次等位基因频率（MAF）>0.05的SNP。我们调查32个SNP，这些SNP的次等位基因频率≥0.05，分布于4q22.1区域的rs6532023位点上游20 kb到下游20 kb之间。此位点在欧洲群体研究中报道过与OP有明显关联性。应用Sequenom MassARRAY基因分型技术，在样本中对上述位点与 BMD及PMOP的易感性进行关联验证。结果 本研究随机收集440例病例样本和640例正常对照样本，结果发现在我们的样本中rs6532023与BMD及OP具有显著关联性（P=0.015），等位基因G是疾病易感因子，而T为保护因子。进一步的基因型关联分析也得出了相似的结论（P=0.040）。单倍型分析发现，此区域的一个单倍域rs7683315-rs6532023-rs1471400-rs1471403与BMD和OP（P=0.032）相关联，病例组单倍型A-G-G-C群体发病率是正常对照组的1.5倍。结论 目前为止，本文是首次探究汉族群体中4q22.1区多态性与OP的关联性。研究结果证明了4q22.1区对OP发病的影响，4q22.1区可能是BMD和OP的遗传危险因素。 |
| 英文摘要: |
| Objective To explore whether genetic polymorphism in/around susceptibility genes/regions at 4q22.1 region is associated with bone mineral density (BMD) and osteoporosis (OP) susceptibility in postmenopausal women of Han nationality. Methods All the SNPs of region between 20 kb upstream and 20 kb downstream of rs653023 in the HapMap HCB database were screened using Haploview. SNPs with minor allele frequencies (MAF) over 0.05 were selected. Thirty-two SNPs with minor allele frequencies ≥0.05 between 20 kb upstream and 20 kb downstream of rs6532023, mapping in the 4q22.1 region, were investigated. It was reported to be significantly associated with osteoporosis in European studies. Sequenom Mass ARRAY Genotyping System was used to verify candidate genes/loci which were significantly associated with BMD and OP in our samples. Results Samples of 440 cases and 640 controls were randomly collected. We found that rs6532023 was significantly associated with BMD and OP (p=0.015) in our samples. Allele G was a risk factor, but T was a protective factor. Further genotype association analyses suggested a similar pattern (P=0.040). Additionally, haplotype analyses indicated that a haplotype block rs7683315-rs6532023-rs1471400-rs1471403 in the region was associated with BMD and OP (P=0.032), and the risk of haplotype A-G-G-C was 1.5-fold higher than that in normal controls. Conclusion To our knowledge, this is the first report to examine the relationship between 4q22.1 region polymorphism and osteoporosis in Han Chinese. Our results provide evidence that the region of 4q22.1 may be a genetic risk factor of BMD and OP. |
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