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目的寻找汉族人群中后纵韧带骨化(OPLL)患者4个候选基因的多态性位点,对与疾病相关的位点进行研究。方法应用Sequnom系统对180例汉族人群4个候选基因(COL6A1、BMP-2、VDR和Runx2)共19个SNP进行分析,病例组78例,对照组102例,对比两组中每个SNP的基因型分布频率与等位基因分布频率,分析研究与OPLL发病相关的多态性位点及其相互关系。结果在筛选的4个候选基因共19个SNP位点中,等位基因分析未发现与疾病相关的位点。基因分型差异位点发现Runx2基因的2个位点(rs1321075与rs12333172)在疾病组与对照组差异有统计学意义(P=0.033 9,P=0.042 8),且两个位点均位于6号染色体上,连锁不平衡分析(LD分析)发现位点与疾病之间存在连锁不平衡;6号染色体上的11个SNP位点形成了2个分别长达51kb和21kb的单倍体域,其中由rs967588、rs16873379、rs3749863、rs6908650形成的单倍体域CTCG在病例组与对照组发生比值为1.75,风险比0.81,表明有可能增加疾病发生比率(P=0.259)。COL6A1、BMP-2、VDR基因未发现与疾病显著相关的多态性位点。结论本研究首次报道汉族人群中OPLL患者Runx2基因中SNP的变化可能导致OPLL,而COL6A1、BMP-2、VDR基因中的多态性位点未显现出与疾病显著相关。
Objective To search for the polymorphism sites of four candidate genes in patients with posterior longitudinal ligament ossification (OPLL) in Chinese Han population and to study the disease-related sites. Methods Sequnom system was used to analyze 19 SNPs of four candidate genes (COL6A1, BMP-2, VDR and Runx2) in 180 Chinese Han population. There were 78 cases in the case group and 102 cases in the control group. Type distribution frequency and allele distribution frequency analysis of OPLL pathogenesis-related polymorphic sites and their relationship. Results In the 19 SNPs selected from the 4 candidate genes, allele analysis found no disease-related sites. Two genotypes of Runx2 gene (rs1321075 and rs12333172) were found to be significantly different in the disease group and the control group (P = 0.033 9, P = 0.042 8), and both loci were located at 6 On the chromosome, linkage disequilibrium analysis (LD analysis) showed that there was a linkage disequilibrium between loci and disease. Eleven SNPs on chromosome 6 formed two haplotype domains of up to 51kb and 21kb respectively, The haplotype CTCG haplotype formed by rs967588, rs16873379, rs3749863 and rs6908650 had a ratio of 1.75 in the case group to the control group with a risk ratio of 0.81, indicating that it is possible to increase the incidence of the disease (P = 0.259). COL6A1, BMP-2, VDR gene found no significant correlation with the disease polymorphic sites. Conclusions This study reports for the first time that changes in SNPs in Runx2 gene in OPLL patients in Han population may lead to OPLL. However, polymorphisms in COL6A1, BMP-2 and VDR genes were not significantly associated with disease.