Glaucoma is a polygenic neurodegenerative disease and the second most common cause of blindness in Saudi Arabia. To test the hypothesis that genetic variants in the genes involved in the bone morphogenic protein (BMP) signaling pathway may be associated with glaucoma, we investigated the association between 3′ untranslated region variants, rs12997 in ACVR1 and rs1043784 in BMP6, and primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG). In a case-control study, TaqMan® real-time PCR-based genotyping was done in 444 subjects consisting of 250 controls, 101 PACG and 95 PXG cases, and tested for genetic association with glaucoma-types and other clinical phenotypes. Rs12997[G] allele in ACVR1 exhibited significant 2-fold increased risk of PACG (p = 0.005) in women but not in men. Similarly, genotype analysis also showed that subjects carrying rs12997[G/G] genotype were at > 2-fold risk of PACG that remained significant after adjustment for age, sex, and Bonferroni correction in the recessive model. Furthermore, this effect was also significant in women only. In PXG, the rs12997[G/G] genotype showed a significant trend towards increased risk of the disease (OR = 2.04, 95% CI = 0.99–4.18, p = 0.049) but did not survive the Bonferroni correction. Regression analysis showed that rs12997[G/G] genotype was a significant predictor of PACG independent of age, sex, and rs1043784 genotypes. Likewise, age and rs12997[G/G] genotype showed significant effect on PXG outcome. The rs12997[A/G] genotype showed significant association with cup/disc ratio as compared to wild-type (p = 0.005) in PXG. Genotype and allele frequencies of rs1043784 in BMP6 did not show any significant association either with PACG or PXG. Our results suggest that the polymorphism rs12997 in the ACVR1 gene involved in the BMP signaling pathway is significantly associated with PACG and PXG in a Saudi cohort. This is the first study to associate this variant/gene with PACG and PXG. However, further studies would be needed to replicate these findings in a large population-based cohort.

中文翻译：

---

沙特阿拉伯原发性闭角型和假性剥脱性青光眼患者ACVR1多态性rs12997和BMP6基因rs1043784多态性与骨形态发生蛋白信号通路有关。

青光眼是一种多基因神经退行性疾病，是沙特阿拉伯失明的第二大最常见原因。为了测试有关骨形态发生蛋白（BMP）信号通路中基因的遗传变异可能与青光眼有关的假设，我们研究了3'非翻译区变异，ACVR1中的rs12997和BMP6中的rs1043784与原发性角闭合性青光眼（PACG）和假性剥脱性青光眼（PXG）。在一项病例对照研究中，对444名受试者（包括250名对照，101名PACG和95名PXG病例）进行了基于TaqMan®实时PCR的基因分型，并测试了与青光眼类型和其他临床表型的遗传关联。在女性中，ACVR1中的Rs12997 [G]等位基因显示出PACG风险显着增加2倍（p = 0.005），而男性则没有。同样，基因型分析还显示，携带rs12997 [G / G]基因型的受试者处于PACG的> 2倍风险，在隐性模型中调整了年龄，性别和Bonferroni校正后，PACG的风险仍然很高。此外，这种作用仅在女性中也很明显。在PXG中，rs12997 [G / G]基因型显示出增加患病风险的显着趋势（OR = 2.04，95％CI = 0.99-4.18，p = 0.049），但没有在Bonferroni矫正中幸免。回归分析表明，rs12997 [G / G]基因型是PACG的重要预测因子，与年龄，性别和rs1043784基因型无关。同样，年龄和rs12997 [G / G]基因型对PXG结局显示显着影响。与PXG中的野生型（p = 0.005）相比，rs12997 [A / G]基因型与杯/盘比率显着相关。BMP6中rs1043784的基因型和等位基因频率与PACG或PXG均未显示任何显着关联。我们的结果表明，在沙特阿拉伯队列中，参与BMP信号通路的ACVR1基因多态性rs12997与PACG和PXG显着相关。这是第一项将该变体/基因与PACG和PXG相关联的研究。然而，将需要进一步的研究来在一个以人口为基础的大型队列中复制这些发现。