DataSheet1_Evaluation of ABCA1 and FNDC3B Gene Polymorphisms Associated With Pseudoexfoliation Glaucoma and Primary Angle-Closure Glaucoma in a Saudi Cohort.PDF

Objective: It is plausible that common disease mechanisms exist in glaucoma pathophysiology. Accordingly, we investigated the genetic association of two previously reported primary open-angle glaucoma (POAG)-related gene polymorphisms, rs2472493 (A > G) in ABCA1 and rs7636836 (C > T) in FNDC3B, in primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG).
Methods: TaqMan genotyping was performed in a total of 442 subjects consisting of 246 healthy controls, 102 PACG patients, and 94 PXG patients. Statistical evaluations were performed to detect allelic and genotype association of the variants with the disease and clinical variables such as intraocular pressure (IOP) and cup/disc ratio.
Results: Overall, there was no allelic or genotype association of these variants in PACG and PXG. However, rs7636836[T] allele significantly increased the risk of PXG among men (p = 0.029, odds ratio [OR] = 2.69, 95% confidence interval = 1.11–6.51). Similarly, rs2472493 and rs7636836 genotypes also showed significant association with PXG among men in over-dominant model (p = 0.031, OR = 1.98, 95% CI = 1.06–3.71) and co-dominant model (p = 0.029, OR = 2.69, 95% CI = 1.11–6.51), respectively. However, none survived Bonferroni’s correction. Besides, the synergic presence of rs2472493[G] and rs7636836[T] alleles (G-T) was found to significantly increase the risk of PACG (p = 0.026, OR = 2.85, 95% CI = 1.09–7.46). No significant genotype influence was observed on IOP and cup/disc ratio.
Conclusion: Our results suggest that the polymorphisms rs2472493 in ABCA1 and rs7636836 in FNDC3B genes may be associated with PXG among men, and a G-T allelic combination may confer an increased risk of PACG in the middle-eastern Saudi cohort. Further research in a larger population-based sample is needed to validate these findings.

现有研究认为，青光眼的病理生理过程存在共同的疾病机制。据此，本研究针对原发性闭角型青光眼（primary angle-closure glaucoma, PACG）与假性剥脱性青光眼（pseudoexfoliation glaucoma, PXG），探究了此前已报道的两种原发性开角型青光眼（primary open-angle glaucoma, POAG）相关基因多态性的遗传关联：即ABCA1基因的rs2472493（A>G）位点与FNDC3B基因的rs7636836（C>T）位点。
方法：本研究共纳入442名受试者，其中246名为健康对照者，102名为PACG患者，94名为PXG患者。采用TaqMan基因分型技术完成所有受试者的基因分型。通过统计学分析，检测上述变异位点与疾病及眼压（intraocular pressure, IOP）、杯盘比（cup/disc ratio）等临床指标的等位基因和基因型关联。
结果：整体而言，上述变异位点在PACG与PXG群体中未呈现显著的等位基因或基因型关联。但在男性亚组中，rs7636836[T]等位基因可显著升高PXG的发病风险（p=0.029，比值比（odds ratio, OR）=2.69，95%置信区间（confidence interval, CI）=1.11–6.51）。类似地，在超显性遗传模型下，rs2472493基因型与男性PXG发病显著相关（p=0.031，OR=1.98，95%CI=1.06–3.71）；在共显性遗传模型下，rs7636836基因型与男性PXG发病显著相关（p=0.029，OR=2.69，95%CI=1.11–6.51）。不过上述关联均未通过邦费罗尼校正。此外，研究发现rs2472493[G]与rs7636836[T]等位基因的协同组合（G-T）可显著升高PACG的发病风险（p=0.026，OR=2.85，95%CI=1.09–7.46）。未观察到基因型对眼压及杯盘比存在显著影响。
结论：本研究结果表明，ABCA1基因的rs2472493位点与FNDC3B基因的rs7636836位点多态性可能与男性群体的PXG发病相关，而G-T等位基因组合可能会增加中东沙特队列人群患PACG的风险。未来需在更大规模的人群队列中开展研究以验证本研究结果。