国人骨形态发生蛋白-2基因多态性与颈椎后纵韧带骨化的遗传关联研究

Association of bone morphogenetic protein-2 gene polymorphisms with susceptibility to ossification of the posterior longitudinal ligament of the cervical spine in Chinese patients

目的 探讨国人骨形态发生蛋白-2（BMP-2）基因编码区单核苷酸多态性（SNPs）位点与颈椎后纵韧带骨化（OPLL）的遗传易感性和骨化程度的关系。方法 临床收集OPLL病例420例,对照组506例,采用直接测序法对目的基因片段进行序列分析,进而对BMP-2基因编码区SNPs位点进行分型,比较不同基因型和等位基因的分布差异。结果 BMP-2基因外显子2上的Ser37Ala（T/G）的TT、TG、GG基因型分别为752例（81%）、174例（19%）、0例,基因型分布在病例组与对照组间差异有统计学意义（P〈0.01）,TG基因型与OPLL的发生有关。外显子3上的Arg190Ser（A/T）的AA、AT、TT基因型分别为228例（24%）、464例（50%）、234例（26%）,基因型分布在病例组与对照组间差异有统计学意义（P〈0.01）,AT基因型与OPLL的发生有关。对OPLL患者外显子2上的Ser87Ser（A/G）基因型分析发现,GG基因型的OPLL患者其骨化椎体的数量明显多于AG和AA基因型（P〈0.05）,表明G等位基因能够加重OPLL患者的严重程度,A等位基因能够限制OPLL患者异位骨化的发生。结论 BMP-2基因外显子2上的Ser37Ala（T/G）和外显子3上的Arg190Ser（A/T）多态性与OPLL的发生相关。BMP-2基因外显子2上的Ser87Ser（A/G）基因型与OPLL的严重程度有关。BMP-2是OPLL的易感基因。

Objective To investigate the association of single nucleotide polymorphism （SNPs） of bone morphogenetic protein-2 （BMP-2） gene encoding region with susceptibility to ossification of the posterior longitudinal ligament （OPLL） of cervical spine and its severity in Chinese patients. Methods A total of 420 OPLL patients and 506 age-and sex-matched controls were studied. Genomic DNA was isolated from venous blood and polymerase chain reaction （PCR） was performed with a standerd protocol. The PCR products were analyzed by direct sequencing. To compare the genotypic and allelic distribution between OPLL cases and control subjects. Results The number of subjects in the total study population with the Ser37Ala （T/G）TY, TG and GG genotypes was 752, 174 and O, respectively, with frequencies of 81%, 19% and O, respectively. There was a statistical difference between OPLL cases and control subjects （P 〈 0. 001 ）, The TG genotype was associated with the occurrence of OPLL. The number of subjects in the total study population with the Argl90Ser （A/T） AA, AT and TT genotypes was 228,464 and 234, respectively, with frequencies of 24%, 50% and 26%, respectively. There was a statistical difference between OPLL cases and control subjects （ P 〈 0. 01 ）, The AT genotype was associated with the occurrence of OPLL. For the Ser87Ser （A/G） polymorphism, patients with G allele had a significantly greater number of ossified vertebrae compared with patients without A allele. Conclusion The Ser37Ala （T/G） polymorphism in exon2 and the Argl90Ser （A/T） polymorphism in exon3 of BMP-2 gene are associated with the occurrence of OPLL. The Ser87Ser （A/G） polymorphism in exon2 of BMP-2 gene is associated with more extensive OPLL. BMP-2 gene is the susceptibility geue of OPLL.