RASGRF1基因遗传多态性与甘肃地区近视易感性的相关性  

Study on the Association between RASGRF1 Genetic Polymorphisms and Myopia Susceptibility in Gansu Province

作　　者：汪向利[1] 杨丽媛 金庸 李培强[2] 丁韵涵 谢小冬[2] 杨君[1] Xiangli Wang;Liyuan Yang;Yong Jin;Peiqiang Li;Yunhan Ding;Xiaodong Xie;Jun Yang(Optometry Center,Gansu Provincial Hospital,Lanzhou 700030,China;School of Basic Medical Sciences,Lanzhou University,Lanzhou 730000,China)

机构地区：[1]甘肃省人民医院眼视光中心,兰州700030 [2]兰州大学基础医学院,兰州730000

出　　处：《中华眼视光学与视觉科学杂志》2022年第3期198-207,共10页Chinese Journal Of Optometry Ophthalmology And Visual Science

基　　金：甘肃省自然科学基金(17JR5RA039)。

摘　　要：目的:分析RASGRF1基因顺式调控元件中单核苷酸多态性与甘肃地区近视人群的相关性。方法:系列病例对照研究。选取2018年1月至2019年1月就诊于甘肃省人民医院眼视光学中心的高度近视患者166例(332眼)和中低度近视患者92例(184眼)分别作为高度近视组和中低度近视组,并将77例(154眼)无近视的志愿者作为正常对照组。首先利用"DNA元件百科全书"计划(ENCODE)和基因型组织表达数据库(GTEx)确定眼组织细胞相关功能性调控元件中的5个单核苷酸多态性(SNP),并利用多重连接酶检测反应技术进行候选SNP的基因分型。在不同遗传模式下,采用卡方检验、非条件Logistic回归分析近视患者和正常对照人群的基因型频率分布差异。结果:rs8033417 T/C在显性模式下含等位基因C的个体近视的发病风险明显降低(P=0.035);rs8033417与甘肃地区中低度近视发病风险无相关性,但在显性模式和加性模式下能明显降低高度近视患者的患病风险(P=0.043、0.032)。进一步的生物信息学分析发现,rs8033417 T/C与RASGRF1基因的反义长非编码RNA基因RP11-16K12.1的表达相关。结论:rs8033417可能是甘肃地区近视发生相关的遗传变异位点,推测其可能通过影响反义长非编码RNA基因RP11-16K12.1的表达,继而调控RASGRF1基因表达从而影响近视尤其是高度近视的患病风险。Objective:To analyze the association between the SNPs in the cis-regulatory elements of the RASGRF1 gene and myopia patients in Gansu province.Methods:In a prospective case-control study,166 patients with high myopia(332 eyes),92 patients with moderate and low myopia(184 eyes)and 77 people from a normal control population(154 eyes)were enrolled in the Optometry Center,Gansu Provincial Hospital from January 2018 to January 2019.Five SNPs were identified using ENCODE and GTEx,and candidate SNPs were genotyped using a multiple ligase detection reaction technique.A Chi-square test and unconditional logistic regression were used to analyze the differences in genotype frequency distribution between the myopia patients and the normal control population under different genetic patterns.Results:Rs8033417 T/C allele C significantly reduced the risk of myopia in the dominant mode(P=0.035).Rs8033417 had no significant correlation with the risk of moderate and low myopia in Gansu,but it significantly reduced the risk of high myopia(P=0.043,0.032).Further bioinformatics analysis showed that rs8033417 T/C was correlated with the expression of RP11-16K12.1,the antisense long non-coding RNA of the RASGRF1 gene.Conclusion:Rs8033417 may be a genetic variation locus associated with myopia in Gansu province.It is speculated that rs8033417 may affect the risk of myopia,especially high myopia,by affecting the expression of the antisense long non-coding RNA gene RP11-16K12.1 and then regulating the expression of the RASGRF1 gene.

关 键 词：近视 RASGRF1 RP11-16K12.1 单核苷酸多态性 长链非编码RNA 

分 类 号：R778.11[医药卫生—眼科]