青海地区藏族人群原发性闭角型青光眼相关多基因单核甘酸多态性分析研究

The prevalence of primary angle closure glaucoma (PACG) has been suggested to be associated with race, region, gender and environment factors. PACG behaves differently in various races; it has been recognized that beside the many environmental and other physiologic factors to PACG, there is also a significant genetic contribution. Recent investigations on PACG have been focused on the population of Caucasian and Han Chinese people of southern China; whereas, study on identification of underlying genetic etiology of PACG in people of Tibetan descent who are residents in Qing-Tibet areas with specific geographic and environmental characteristics has been previously less performed. The further investigation on PACG of Tibetans therefore would be essential to clarify whether the genetic variation contributes to the pathogenisis of PACG in different races. Our study will investigate the single-nucleotide polymorphisms (SNPs) of selected genes associated with adjusting extracellular matrix, ocular axial length, pupil constrict muscle and oxidative stress, which probably involved in variant mechanisms of PACG by using molecular and genetic techniques including DNA extraction, PCR amplification, polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） assay, to further evaluate whether genetic variation in these genes is associated with PACG in the Qinghai Tibetans, and determine the susceptible genes as the risk factors with onset of PACG in Tibetan population.

原发性闭角型青光眼(primary angle closure glaucoma, PACG)患病率与种族、地域、性别以及环境有关，而遗传基因也是不容忽视的因素。近年来国内外对于PACG相关基因分析主要集中在白种人以及我国南方汉族人群，而对于世居在具有独特地理气候环境的青藏地区的藏族人群PACG的患病率及相关基因鲜有研究。探讨藏族人群PACG发病特点，将为阐明PACG人种患病基因差异性具有一定的意义。因此我们选择与PACG不同发病因素相关基因，即调节细胞外基质、眼轴、瞳孔括约肌、以及氧化应激相关基因来研究藏族人群PACG的易感基因，从分子基因水平，以聚合酶链反应-限制性片段长度多态性方法分析筛选基因多态性，以期发现藏族人群PACG的易感基因以及不同基因型与PACG风险的关系。

原发性闭角型青光眼(primary angle closure glaucoma, PACG)患病与种族、地域、性别以及环境有关。我们选择与PACG不同发病因素相关基因，即调节细胞外基质（Extracellular matrix, ECM）、眼轴以及氧化应激相关基因来研究青海藏族人群PACG的易感基因，从分子基因水平，以聚合酶链反应-限制性片段长度多态性方法分析筛选基因多态性，探讨藏族人群PACG的易感基因以及不同基因型与PACG风险的关系。我们的研究结果表明青海地区藏族人群PAGC患病率为1.02%。细胞外基质相关的MMP9的单核苷酸多态性rs17576和rs1043209与青海藏族PACG的易感性有关（分别为P=0.012、P=0.015），PACG组的TIMP-1基因rs4898与对照组无明显差异（P=0.691），与眼轴相联系的HGF基因rs5745718与对照组相比有统计学差异（P=0.015)，而HGF基因rs12536657及CHX10的单核苷酸多态性rs3814762与PACG的易感性无关（分别为P=0.408、P=0.383）。PACG组DNA修复基因XRCC1 rs25487与PACG的易感性有关（P=0.03)，而XPD基因rs13181、MTHFR的单核苷酸多态性rs1801131与rs1801133的基因型频率与对照组相比无统计学差异（分别为P=0.662、P=0.25、P=0.8）。PACG患者8-OHdG活性升高，与对照组相比有统计学意义（107.484±12.819 vs 97.244±15.642ng/L；P<0.05）；TAS水平下降，亦有统计学差异（13.392±2.583 vs 14.889±2.282U/ml；P<0.05）。在本研究中与调节ECM、眼轴及DNA修复基因如MMP9 rs17576和rs1043209, HGF rs5745718以及XRCC1 rs25487可能为青海藏族人群PACG的易感基因。探讨世居在具有独特地理气候环境的青藏地区的藏族人群PACG的基因特点，为阐明PACG人种患病基因差异性具有一定的意义。