摘要
Functional studies have suggested the important role of early growth response I （EGR1） and Laminin a2- chain （LAMA,？.） in human eye development. Genetic studies have reported a significant association of the single nu- cleotide polymorphism （SNP） in the LAMA2 gene with myopia. This study aimed to evaluate the association of the tagging SNPs （tSNPs） in the EGR1 and LAMA2 genes with high myopia in two independent Han Chinese populations. Four tSNPs （rs11743810 in the EGR1 gene; rs2571575, rs9321170, and rs1889891 in the LAMA2 gene） were se- lected, according to the HapMap database （http：//hapmap.ncbi.nlm.nih.gov）, and were genotyped using the ligase detection reaction （LDR） approach for 167 Hart Chinese nuclear families with extremely highly myopic offspring （〈-10.0 diopters） and an independent group with 485 extremely highly myopic cases （〈-10.0 diopters） and 499 con- trois. Direct sequencing was used to confirm the LDR results in twenty randomly selected subjects. Family-based association analysis was performed using the family-based association test （FBAT） software package （Version 1.5.5）. Population-based association analysis was performed using the Chi-square test. The association analysis power was estimated using online software （http：lldesign.cs.ucla.edu）. The FBAT demonstrated that all four tSNPs tested did not show association with high myopia （P〉0.05）. Haplotype analysis of tSNPs in the LAMA2 genes also did not show a significant association （P〉0.05）. Meanwhile, population-based association analysis also showed no significant asso- ciation results with high myopia （P〉0.05）. On the basis of our family- and population-based analyses for the Han Chinese population, we did not find positive association signals of the four SNPs in the LAMA2 and EGR1 genes with high myopia.
目的:检测分析EGR1和LAMA2基因序列中单核苷酸多态性位点(SNP)在中国汉族人病理性高度近视的遗传机制中的作用。创新点:检测了EGR1基因外显子序列中的SNP,验证了其与高度近视发病无关联;检测了LAMA2基因中热点区域中的三个SNP,发现在我国汉族人群中,这几个SNP与高度近视发病的遗传机制无关,与先前国外报道结果不同。方法:收集167个高度近视核心家系以及485例散发高度近视患者和499例正视眼对照者。根据Hap Map单倍型数据库以及先前的研究结果选择标签SNP(图1和2),测定所收集患者的相应基因型,采用Haploview和卡方分析软件作关联分析,并以关联分析效能软件计算本研究的计算效能(表3和4)。结论:本研究在汉族人高度近视人群中未检测到阳性关联信号,需要进一步的研究深入验证。
基金
Project supported by the Natural Science Foundation of Zhejiang Province(No.LY14H120003)
the Qianjiang Talent Project of Zhejiang Province(No.2013R10040),China
