VDR基因单核苷酸多态性与慢性阻塞性肺疾病并发骨质疏松的关系

Association of VDR gene polymorphism with osteoporosis in patients with chronic obstructive pulmonary disease

目的 探讨中国北方汉族人群维生素D受体(VDR)基因单核苷酸多态性与慢性阻塞性肺疾病(COPD)并发骨质疏松的关系。方法 回顾2007年9月-2017年10月收治的COPD急性加重住院患者379例资料,分为非骨质疏松组155例与骨质疏松组224例,提取全血样本的基因组DNA。利用UCSC基因组浏览器和Haploview 4.2软件确定VDR基因的标签单核苷酸多态性(tagSNP)。应用Sequenom MassARRAY SNP检测技术对VDR基因的tagSNP进行基因型分析。采用Logistic回归方法研究其共显性、显性、隐性等遗传模式下各SNP的比数比(OR值)和置信区间(CI),评估VDR基因单核苷酸多态性与COPD并发骨质疏松的关系。结果 两组在性别、年龄、是否饮酒、外周血血小板计数、血磷、血肌酐等参数上差异均有统计学意义(P<0.05)。在筛选出的VDR基因17个tagSNPs(rs2238140 G/A,rs2228570 G/A,rs2408877A/T,rs12721370 C/A,rs7299460 T/C,rs2239184 G/A,rs2239186 A/G,rs7136534 C/T,rs12721364 G/A,rs2853561C/T,rs7965943 T/G,rs11168287 G/A,rs11608702 T/A,rs2239179 T/C,rs2189480 T/G,rs59707231 T/A,rs2853559C/T)中,rs2853561携带T/C和T/T基因型的COPD患者,发生骨质疏松的风险较C/C更低(在显性遗传模式下,T/C+T/T vs.C/C,OR=0.34,95%CI 0.18~0.63,P=0.0003539),差异有统计学意义。结论 VDR基因中的rs2853561与COPD并发骨质疏松之间存在相关性。VDR基因单核苷酸多态性在COPD并发骨质疏松发病机制中的具体作用有待进一步研究。

Objective To investigate the relationship between single nucleotide polymorphism of vitamin D receptor(VDR)genes and osteoporosis in Chinese Northern Han patients with chronic obstructive pulmonary disease(COPD).Methods Patients with acute exacerbation COPD were enrolled and divided into osteoporosis and non-osteoporosis groups.Genomic DNA was extracted from peripheral blood of the subjects.UCSC genome browser and haploview 4.2 software were used to screen the tag single nucleotide polymorphism(tagSNPs)of VDR gene.The selected tagSNPs of VDR gene were genotyped by Sequenom MassARRAY SNP platform.Logistic regression was used to analyze the OR values and confidence intervals(CI)of each tagSNP in the codominant,dominant and recessive genetic models,and assess the relationship between single nucleotide polymorphisms in VDR gene and osteoporosis in COPD patients.Results A total of 379 COPD patients were enrolled.The group of osteoporosis and non-osteoporosis differed significantly in gender,age,alcohol assumption,peripheral platelet counts,serum phosphorus and serum creatinine levels(P<0.05).Finally,17 tagSNPs of VDR gene(rs2238140 G/A,rs2228570 G/A,rs2408877 A/T,rs12721370 C/A,rs7299460 T/C,rs2239184 G/A,rs2239186 A/G,rs7136534 C/T,rs12721364 G/A,rs2853561 C/T,rs7965943 T/G,rs11168287 G/A,rs11608702 T/A,rs2239179 T/C,rs2189480 T/G,rs59707231 T/A,rs2853559 C/T)were filtered out for association analysis.Patients of rs2853561 carrying T/C and T/T genotypes had a lower risk of developing osteoporosis than those carrying C/C genotype in COPD patients(in dominant mode:T/C+T/T vs.C/C,OR=0.34,95%CI 0.18-0.63,P=0.0003539)with statistical significance.Conclusions The present study has revealed significant relationship between rs2853561 of VDR gene and osteoporosis in patients with COPD.Further studies are needed to discover the mechanism of VDR gene polymorphism in the pathogenesis of osteoporosis in COPD.