Lumi Xhevat, Jelen Mateja M, Jevšinek Skok Daša, Boštjančič Emanuela, Ravnik-Glavač Metka, Hawlina Marko, Glavač Damjan
Eye Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
J Ophthalmol. 2018 May 15;2018:8761625. doi: 10.1155/2018/8761625. eCollection 2018.
The present study investigated the distribution of genotypes within single nucleotide polymorphisms (SNPs) in genes, related to PVR pathogenesis across European subpopulations. Genotype distributions of 42 SNPs among 96 Slovenian healthy controls were investigated and compared to genotype frequencies in 503 European individuals (Ensembl database) and their subpopulations. Furthermore, a case-control status was simulated to evaluate effects of allele frequency changes on statistically significant results in gene-association studies investigating functional polymorphisms. In addition, 96 healthy controls were investigated within 4 SNPs: rs17561 (), rs2069763 (), rs2229094 (), and rs1800629 () in comparison to PVR patients. Significant differences ( < 0.05) in distribution of genotypes among 96 Slovenian participants and a European population were found in 10 SNPs: rs3024498 (), rs315952 (), rs2256965 (), rs2256974 (), rs909253 (), rs2857602 (), rs3138045 (), rs3138056 (), rs7656613 (), and rs1891467 (), which additionally showed significant differences in genotype distribution among European subpopulations. This analysis also showed statistically significant differences in genotype distributions between healthy controls and PVR patients in rs17561 of the gene (OR, 3.00; 95% CI, 0.77-11.75; = 0.036) and in rs1800629 of the gene (OR, 0.48; 95% CI, 0.27-0.87; = 0.014). Furthermore, we have shown that a small change (0.02) in minor allele frequency (MAF) significantly affects the statistical value in case-control studies. In conclusion, the study showed differences in genotype distributions in healthy populations across different European countries. Differences in distribution of genotypes may have had influenced failed replication results in previous PVR-related SNP-association studies.
本研究调查了与欧洲不同亚人群增殖性玻璃体视网膜病变（PVR）发病机制相关基因中，单核苷酸多态性（SNP）内基因型的分布情况。对96名斯洛文尼亚健康对照者中42个SNP的基因型分布进行了研究，并与503名欧洲个体（Ensembl数据库）及其亚人群的基因型频率进行了比较。此外，模拟病例对照状态，以评估等位基因频率变化对研究功能性多态性的基因关联研究中统计学显著结果的影响。另外，对96名健康对照者和PVR患者进行了4个SNP的研究，这4个SNP分别为rs17561、rs2069763、rs2229094和rs1800629。在10个SNP中发现，96名斯洛文尼亚参与者和欧洲人群之间基因型分布存在显著差异（P<0.05），这10个SNP分别为rs3024498、rs315952、rs2256965、rs2256974、rs909253、rs2857602、rs3138045、rs3138056、rs7656613和rs1891467，这些SNP在欧洲亚人群中基因型分布也存在显著差异。该分析还显示，在基因的rs17561（比值比，3.00；95%置信区间，0.77 - 11.75；P = 0.036）和基因的rs1800629（比值比，0.48；95%置信区间，0.27 - 0.87；P = 0.014）中，健康对照者与PVR患者的基因型分布存在统计学显著差异。此外，我们还表明，次要等位基因频率（MAF）的微小变化（0.02）会显著影响病例对照研究中的统计P值。总之，该研究显示了不同欧洲国家健康人群中基因型分布的差异。基因型分布的差异可能影响了先前与PVR相关的SNP关联研究中复制失败的结果。
