原发性开角型青光眼伴高度近视的多基因多位点单核苷酸多态性分析

Single nucleotide polymorphism analysis of multi-loci and -genes in primary open-angle glaucoma with pathological myopia

目的：研究原发性开角型青光眼（POAG）相关的异常单核苷酸多态性（SNP）位点和等位基因，以便早期基因诊断和早期筛选POAG高危人群。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POAG9例，POAG伴高度近视9例，和正常对照100例IL-6，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），和E-选择素（E-Sel）基因的单核苷酸多态性位点。结果：POAG和POAG伴高度近视患者呈多达5～6个位点的SNP改变，包括IL-6R，DRD2和FGB基因的错义表达。其中1例POAG伴高度近视患者呈现唯一的DRD2A等位基因和唯一的IL-6R基因错义表达SNP。同时，POAG和POAG伴高度近视患者表现多个SNP等位基因的异常频率。结论：IL-6，IL-6R，PPARG，E-Sel，TGF-β1，FGB和DRD2基因的SNP在POAG的发生与发展中起着相关联的作用。其中，DRD2的SNP基因类型可能与POAG伴高度近视有关。

AIM： To discover loci and al polymorphism （ SNP ） related glaucoma （ POAG ） for early eles of single nucleotide to primary open-angle screening of high-risk population. METHODS： SNP alleles of interleukin-6 （IL-6）, IL-6 receptor （IL-6R）, dopamine D2 receptor （DRD2）, betafibrinogen （ FGB ）, peroxisome proliferator-activated receptor-y2 （PPARG）, transforming growth factor-β1 （TGF-β1）, and E-selectin （E-Sel） gene in POAG patients （ n = 9）, POAG patients with pathological myopia （ n = 9）, and normal （n = 100） group were measured with ABI Prism 7500HT Fluorescence Quantitative PCR and TaqMan SNP Genotyping fluorescence probe kit. RESULTS： In POAG and POAG with pathological myopia patients, SNP changes of up to 5-6 loci were found, including missense expression of IL-6R, DRD2 and FGB. In one POAG with pathological myopia patient, DRD2 A allele type and IL-6R missense expression were presented together. Meanwhile, a number of SNP allele frequencies were higher or lower in POAG and POAG with pathological myopia patients than those in normal controls. CONCLUSION： The abnormal SNP alleles in IL-6, IL-6R and PPARG genes that are related to glaucomatous retinal and optic nerve damages, E-Sel and TGF-β1 genes that are related to trabecular functions, FGB gene that is related to ischemic optic neuropathy and retinal damages, and DRD2 gene that regulates intraocular pressure and axial growth, play important roles in pathogenesis and development of POAGo These roles might be associated with each other. Particularly, the SNP of DRD2 might be related to POAG with pathological myopia.