摘要目的：探讨骨保护素（ osteoprotegerin）基因多态性与缺血性脑梗死病因亚型的相关性，并初步探讨骨保护素基因多态性与脑动脉粥样硬化（ atherosclerosis， AS）血管损伤程度及部位的关系。方法按照TOAST病因分型选择大动脉粥样硬化型（ large-artery atherosclerosis， LAA）脑梗死患者285例、小动脉闭塞型（ small-artery occlusion， SAO）脑梗死患者91例、单纯脑动脉粥样硬化患者42例及同期健康对照者165名，并将LAA组分别按照脑动脉狭窄支数、颅内／外动脉狭窄情况分为不同亚组。选择骨保护素基因的3个单核苷酸多态性位点（rs2073617、rs3134069、rs3102735），应用聚合酶链反应限制性片段长度多态性检测骨保护素基因多态性。结果所检骨保护素基因3个单核苷酸多态性位点中，rs3102735在LAA组中C等位基因及其对应的基因型CC／CT频率均明显高于对照组（分别为24.04％、14.85％，44.21％、27.88％，χ2＝10.758、11.804，P＝0.001、0.024），而在SAO组、AS组与对照组间差异无统计学意义。其他2个位点rs2073617、rs3134069的基因型及等位基因分布在各病例组与对照组间比较差异均无统计学意义。3个位点在LAA组各亚组中的分布也未见明显差异。单倍型分析发现C-C-T单倍型在LAA组和SAO组频率均显著低于对照组（分别为0.023、0.017、0.068，χ2＝10.399、5.841，P＝0.001、0.016），而T-A-C在LAA组中频率显著高于对照组（分别为0.043、0.016，χ2＝4.708， P＝0.030）。其他单倍型在病例组与对照组间差异无统计学意义。结论骨保护素基因多态性与LAA型脑梗死相关，但未发现骨保护素基因多态性与AS病变的血管损害程度及部位有关。

abstractsObjective To investigate the relationship between osteoprotegerin ( OPG ) gene polymorphisms and ischemic stroke etiological subtypes, as well as the extent and distribution of cerebral atherosclerosis ( AS) lesions.Methods Patients with ischemic stroke included 285 cases of large-artery atherosclerosis (LAA), 91 cases of small-artery occlusion (SAO) and 42 cases of purely AS, and 165 healthy controls were enrolled in this study.The LAA group was respectively divided into 3 subgroups according to the number and the distribution of stenostic vessels.Genotyping of three single nucleotide polymorphisms (SNPs;rs2073617, rs3134069, and rs3102735) in the promoter region of the OPG gene was performed by polymerase chain reaction-restriction fragment length polymorphism.Results Regarding the three SNPs of OPG gene, the frequence of genotype CC/CT and the prevalence of allele C of rs3102735 were higher in the LAA group contrasting with the control group ( 24.04% vs 14.85%, 44.21% vs 27.88%,χ2 =10.758, 11.804, P =0.001,0.024).However, comparisons of other frequences of genotypes or alleles did not reveal any significant differences among the LAA group, the SAO group, the AS group and the control group, as well as among different subgroups of LAA group.Haplotype analysis revealed that the frequencies of haplotype C-C-T in LAA group and SAO group were significantly lower ( 0.023, 0.017 vs 0.068,χ2 =10.399, 5.841,P=0.001, 0.016), while that of haplotype T-A-C was significantly higher in SAO group(0.043 vs 0.016,χ2 =4.708, P=0.030) compared with controls.Conclusions Our findings indicate that OPG gene polymorphisms might be associated with increased susceptibility to LAA ischemic stroke.But we fail to show association of OPG gene with the extent and distribution of AS.