在中国北方一个队列中，对 8 个原发性闭角型青光眼易感基因座的基因型-眼生物测量相关性进行分析。
Genotype-ocular biometry correlation analysis of eight primary angle closure glaucoma susceptibility loci in a cohort from Northern China.
机构信息
People's Hospital of Ningxia Hui Autonomous Region, Ningxia Eye Hospital (First Affiliated Hospital of Northwest University For Nationalities), Yinchuan, China.
Clinical Medical College of Ningxia Medical University, Yinchuan, China.
出版信息
PLoS One. 2018 Nov 6;13(11):e0206935. doi: 10.1371/journal.pone.0206935. eCollection 2018.
PURPOSE
Recent genome-wide association studies (GWAS) have verified eight genetic loci that were significantly associated with primary angle-closure glaucoma (PACG). The present study investigated whether these variants are associated with the ocular biometric parameters of anterior chamber depth (ACD) and axial length (AL) in a northern Chinese population, as well as whether there were differences in the association of genetic markers in our cohort based on ethnicity.
METHODS
A case-control association study of 500 patients and 720 controls was undertaken. All individuals were genotyped for eight single nucleotide polymorphisms (SNPs) (rs11024102 in PLEKHA7, rs3753841 in COL11A1, rs1015213 located between PCMTD1 and ST18, rs3816415 in EPDR1, rs1258267 in CHAT, rs736893 in GLIS3, rs7494379 in FERMT2, and rs3739821 mapping between DPM2 and FAM102A) using an improved multiplex ligation detection reaction (iMLDR) technique. Allelic and genotypic frequency differences were evaluated using a logistic regression model. Generalized estimation equation (GEE) analysis was conducted for association testing between genotypes and ocular biometric parameters. False discovery rate (FDR) correction for multiple comparisons was employed, and the statistical power was calculated via power and sample size calculation.
RESULTS
Four of the eight SNPs, rs3753841, rs1258267, rs736893 and rs7494379, were associated with PACG (p = 0.007, 0.0016, 0.0045, 0.045, respectively), and only rs3753841, rs1258267 and rs736893 surpassed the FDR correction. For subgroup analysis, only rs1258267 could withstand multiple testing correction in the Han nationality (p = 0.00571). In the GEE tests, rs3753841, rs1258267 and rs736893 were found to be nominally associated with ACD (p = 0.023, 0.016, 0.01, respectively). However, these associations could not survive FDR correction.
CONCLUSIONS
The SNP rs3753841 in COL11A1, rs1258267 in CHAT and rs736893 in GLIS3 are associated with PACG in northern Chinese people, and the association of genetic markers manifests a tendency of ethnic diversity. Larger population-based studies are warranted to reveal additional PACG loci and ethnic aspects of PACG.
目的
最近的全基因组关联研究（GWAS）已经验证了与原发性闭角型青光眼（PACG）显著相关的 8 个遗传位点。本研究旨在探讨这些变异是否与中国北方人群前房深度（ACD）和眼轴长度（AL）的眼部生物测量参数相关，以及我们的队列中基于种族的遗传标记的关联是否存在差异。
方法
采用病例对照关联研究，纳入 500 例患者和 720 例对照。使用改良多重连接检测反应（iMLDR）技术对 8 个单核苷酸多态性（SNP）（PLEKHA7 中的 rs11024102、COL11A1 中的 rs3753841、PCMTD1 和 ST18 之间的 rs1015213、EPDR1 中的 rs3816415、CHAT 中的 rs1258267、GLIS3 中的 rs736893、FERMT2 中的 rs7494379 和 DPM2 和 FAM102A 之间的 rs3739821）进行基因分型。使用逻辑回归模型评估等位基因和基因型频率差异。采用广义估计方程（GEE）分析基因型与眼部生物测量参数之间的关联。采用错误发现率（FDR）校正进行多重比较，并通过功率和样本量计算计算统计效力。
结果
8 个 SNP 中有 4 个（rs3753841、rs1258267、rs736893 和 rs7494379）与 PACG 相关（p = 0.007、0.0016、0.0045 和 0.045），只有 rs3753841、rs1258267 和 rs736893 超过了 FDR 校正。亚组分析显示，只有 rs1258267 在汉族中能够承受多重检验校正（p = 0.00571）。在 GEE 检验中，rs3753841、rs1258267 和 rs736893 与 ACD 呈名义相关（p = 0.023、0.016 和 0.01）。然而，这些关联无法通过 FDR 校正。
结论
COL11A1 中的 rs3753841、CHAT 中的 rs1258267 和 GLIS3 中的 rs736893 与中国北方人群的 PACG 相关，遗传标记的关联表现出种族多样性的趋势。需要更大的基于人群的研究来揭示额外的 PACG 位点和 PACG 的种族差异。
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