目的:检测原发性开角型青光眼(POAG)和代谢综合征相关基因的单核苷酸多态性(SNP),分析代谢综合征作为危险因素在POAG发生发展中所起的可能作用。方法:应用ABI Prism 7500HT型荧光定量PCR仪结合TaqMan SNP Genotyping试剂盒荧光探针技术检测POAG37和正常对照100例白介素6(IL-6)、白介素6受体(IL-6R)、多巴胺受体-D2(DRD2)、β-纤维蛋白原(FGB)、过氧化物酶体增殖物激活受体-γ2(PPARG)、转化生长因子-β1(TGF-β1)、E-选择素(E-Sel)、脂蛋白A-5(APOA5)、C反应蛋白(CRP)、外核苷酸焦磷酸酶/磷酸二酯酶1(ENPP1)、肝脂肪酶(LIPC)、脂联素(ADIPOQ)、对氧磷酯酶-1(PON1)和丝氨酸蛋白酶抑制剂E(SERPINE1)基因的基因型,计算并比较其等位基因频率。结果:POAG组IL-6R,IL-6,FGB,CRP,ENPP1,LIPC,ADIPOQ,PON1和SERPINE1的基因型和等位基因频率与正常对照组差异有显著性统计学意义。其中OR值>2.5的有IL-6,FGB,CRP,ENPP1,LIPC和ADIPOQ。结论:代谢综合征作为POAG的危险因素,可能与其相关基因的基因型和等位基因频率有关。其相应的基因表达及其功能可影响POAG的发生和发展,包括SERPINE1作用于小梁网细胞外基质;ENPP1抑制胰岛素样因子活性,影响小梁网细胞生长;IL-6的内源性视神经保护作用;IL-6,IL-6R,E-Sel参与的自身免疫反应;FGB和LIPC在高粘滞血症中作用;ADIPOQ促进NOS/NO生成;PON1的血管内皮保护作用。

AIM:To analyze single nucleotide polymorphisms (SNP) of primary open angle glaucoma-and metabolic syndrome-related genes in primary open angle glaucoma (POAG),in order to elucidate the roles of metabolic syndrome as a risk factor in POAG progress.METHODS:SNP genotypes and alleles of interleukin-6 (IL-6),IL-6 receptor (IL-6R),dopamine D2 receptor (DRD2),beta-fibrinogen (FGB),peroxisome proliferator-activated receptor-γ2 (PPARG),transforming growth factor-β1 (TGF-β1),E-selectin (E-Sel),apolipoprotein A-5 (APOA5),C-reactive protein (CRP),ectonueleotide pyrophosphatase/ phosphodiesterase 1 (ENPP1),hepatic lipase (LIPC),adiponectin (ADIPOQ),paraoxonase 1 (PON1) and serine protease inhibitor E (SERPINE1) genes in POAG (n= 37) and normal control (n=100) groups were measured with ABI Prism 7900HT Fluorescence Quantitative PCR and TaqMan SNP Genotyping fluorescence probe kit.RESULTS:Genotypes and allele frequencies of IL-6R,IL-6,FGB,CRP,ENPP1,LIPC,ADIPOQ,PON1,and SERPINE1 in total POAG group were significantly different compared to the control group. CONCLUSION:Metabolic syndrome as a risk factor for POAG may be associated with genotypes and allele frequencies of the related genes.The corresponding gene expression and function can affect POAG progress,including roles of SERPINE1 in extracellular matrix,ENPP1 in insulin inhibition,IL-6 in endogenous neuroprotection,IL-6,IL-6R and E-Sel in autoimmune response,LIPC and FGB in blood hyperviscosity syndrome,ADIPOQ in NOS/NO production,PON1 in vascular endothelial protection.

R587;R775

中国广东省2008年广州市中医药、中西医结合科研基金资助（No.2008A47）