中国汉族人群SOX2基因与高度近视的关联研究

Association study of polymorphisms in the SOX2 gene with high myopia in Chinese Han population

目的研究SOX2是否可作为中国汉族人群高度近视的候选基因,寻找与高度近视关联的致病基因位点。方法采用病例-对照关联分析法。将同意参加本研究的83例(160眼)正视者作为对照组,117例(211眼)高度近视患者作为病例组,所有患者均进行详细的眼部检查,并提取外周血白细胞基因组DNA。在中国汉族北京居民的基因型数据库中选取3个标签单核苷酸多态性(single nucleotide polymorphism,SNP)位点,采用SNP直接测序法进行基因分型检测。根据所有样本所得各标签SNP的基因型,计算其基因型和等位基因频率,并使用Bonferroni法进行多重检验矫正;采用χ2检验比较病例组和对照组之间等位基因频率及基因型频率分布是否有差异。结果3个标签SNP位点(rs11915160、rs4575941、rs4459940)的基因型结果在病例组和对照组中都符合Hardy-Weinberg平衡,本研究人群具有一定的代表性。rs4575941位点的基因型频率和等位基因频率在病例组和对照组间的差异均具有统计学意义(P=0.04、0.03),但经Bonferroni法矫正后,两组等位基因频率差异无统计学意义(Pc=0.09);病例组rs4575941位点的等位基因G的频率明显高于对照组,OR值为1.58,等位基因G可能是高度近视的一个危险基因。结论中国汉族人群SOX2基因SNP位点rs4575941与高度近视之间的关联存在可疑性,为了明确相关性,需要进一步扩大样本量,选择合适的多重检验方法,并结合其他手段进行大数据分析。

Objective To investigate whether SOX2 can function as a candidate gene for high myopia in C hinese population in search of the high myopia-related disease-causing gene locus. Methods The case-control association study was applied. A total of 83 emmetropia individuals（ 160 eyes） were enrolled as the control group and 117 patients of high myopia（ 211 eyes） as the case group with obtained approvals prior to the study. All patients had undergone detailed eye examination and genomic D NA extraction from peripheral blood leucocytes. Then,3 single nucleotide polymorphism（ SNP） loci were selected from Beijing residents in C hinese Han population. SNP direct sequencing was employed for genotyping. According to the genotype of each tag SNP（ t SNP） obtained from each sample,the gene frequencies of its genotype and alleles were calculated,follow ed by multiple testing and correcting using Bonferroni methods. χ2 test was utilized to evaluate the significant difference betw een the patients and controls regarding the allele frequency and genotype frequency. Results A total of 3 t SNP loci（ rs11915160,rs4575941 and rs4459940） were found according to Hardy-Weinberg equilibrium. The study population was representative. The genotype frequency and allele frequency on rs4575941 were significantly different betw een the case and control groups（ P = 0. 04,0. 03）. How ever,the difference turned out to be insignificant after correcting by Bonferroni methods（ Pc = 0. 09）. The frequency of allele G on rs4575941 was evidently higher in the case group than that in the control group（ O R= 1. 58）,indicating that allele G might be a risk gene for high myopia. Conclusion It is still in doubt whether SNP locus rs4575941 of SO X2 gene in C hinese population is correlated with high myopia. Further studies are needed for validation with a larger sample size and appropriate multiple testing approaches in combination with other means for big data analytics.