Association of known common genetic variants with primary open angle, primary angle closure, and pseudoexfoliation glaucoma in Pakistani cohorts
Association of known common genetic variants with primary open angle, primary angle closure, and pseudoexfoliation glaucoma in Pakistani cohorts
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发表时间：
2014-11
期刊：
影响因子：
2.2
通讯作者：
Shazia Micheal;Humaira Ayub;M. Khan;Bjorn Bakker;Frederieke E. Schoenmaker-Koller;Mahmood Ali;Farah Akhtar;W. Khan;R. Qamar;A. D. den Hollander
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作者：
Shazia Micheal;Humaira Ayub;M. Khan;Bjorn Bakker;Frederieke E. Schoenmaker-Koller;Mahmood Ali;Farah Akhtar;W. Khan;R. Qamar;A. D. den Hollander
尽管原发性开角型青光眼（primary open angle glaucoma，POAG）、原发性闭角型青光眼（primary angle closure glaucoma，PACG）和假性剥脱性青光眼（pseudoexfoliative glaucoma，PEXG）的病因不同，但一些研究表明，这些类型的青光眼具有重叠的遗传危险因素。因此，本研究的目的是评估最近与POAG相关的遗传变异在巴基斯坦POAG、PACG和PEXG患者队列中不同类型青光眼中的作用。方法采用TaqMan方法对CDKN 2B-AS 1（rs 4977756）、CDKN 2B（rs 1063192）、ATOH 7（rs 1900004）、CAV 1（rs 4236601）、TMCO 1（rs 4656461）和SIX 1（rs 10483727）6个基因变异体进行基因分型。共有513名不相关的青光眼患者（268名POAG患者，125名PACG患者和120名PEXG患者）和233名健康对照者被纳入研究。用卡方检验分析基因型和等位基因相关性。结果与对照组相比，POAG（p=0.003; OR [比值比]=0.57）、PACG（p= 0.009; OR=0.52）和PEXG（p = 0.01; OR=0.54）患者的TMCO 1 rs 4656461 G等位基因频率显著降低。与对照个体相比，在PACG患者中观察到ATOH 7 rs 1900004的T等位基因的频率较低（p=0.03; OR=0.69）。CAV 1 rs 4236601的A等位基因在POAG患者中的频率高于对照组（p=0.008; OR=1.49）。这项研究表明，TMCO 1 rs 4656461变异与巴基斯坦人群中的POAG，PACG和PEXG相关。我们的研究无法证实先前报道的CDKN 2B-AS 1、CDKN 2B和SIX 1变异与任何类型青光眼的相关性。结论总之，我们发现了一致的证据表明TMCO 1、ATOH 7和CAV 1中三种常见变异的显著相关性。
Purpose Despite the different etiology of primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG), and pseudoexfoliative glaucoma (PEXG), several studies have suggested that these forms of glaucoma have overlapping genetic risk factors. Therefore, the aim of this study was to evaluate the role of genetic variants recently associated with POAG in different types of glaucoma in Pakistani POAG, PACG, and PEXG patient cohorts. Methods Six variants in CDKN2B-AS1 (rs4977756), CDKN2B (rs1063192), ATOH7 (rs1900004), CAV1 (rs4236601), TMCO1 (rs4656461), and SIX1 (rs10483727) were genotyped using TaqMan assays. A total of 513 unrelated patients with glaucoma (268 with POAG, 125 with PACG, and 120 with PEXG) and 233 healthy controls were included in the study. Genotypic and allelic associations were analyzed with a chi-square test. Results The frequency of the G allele of TMCO1 rs4656461 was significantly lower in the patients with POAG (p=0.003; OR [odds ratio]=0.57), PACG (p=0.009; OR=0.52), and PEXG (p=0.01; OR=0.54) compared to the control individuals. The T allele of ATOH7 rs1900004 was observed less frequently in the patients with PACG (p=0.03; OR=0.69) compared to the control individuals. The A allele of CAV1 rs4236601 was found more frequently in the patients with POAG (p=0.008; OR=1.49) compared to the control individuals. This study demonstrates that the TMCO1 rs4656461 variant is associated with POAG, PACG and PEXG in the Pakistani population. Our study was unable to confirm previous associations reported for variants in CDKN2B-AS1, CDKN2B, and SIX1 with any type of glaucoma. Conclusions In conclusion, we found consistent evidence of the significant association of three common variants in TMCO1, ATOH7, and CAV1.