Aswa Marwa, Helmy Hazem, Noweir Shahira, Ismail Somaia, Taha AlShaimaa, Atef Azza
Department of Biochemistry, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt.
Department of Glaucoma and Optic Nerve Disease, Research Institute of Ophthalmology, Giza, Egypt.
J Genet Eng Biotechnol. 2022 Aug 29;20(1):126. doi: 10.1186/s43141-022-00400-w.
Primary angle-closure glaucoma (PACG) is one of the major causes of blindness in the Middle East with genetic loci and systemic oxidative stress as potential risk factors. The current case-control study aimed to investigate the associations of rs11024102 in Pleckstrin homology domain-containing family A member 7 (PLEKHA7), rs3753841 in collagen 11 A1 (COL11A1), and the systemic oxidative stress markers with PACG in Egyptian patients. Thirty-five control subjects and 64 PACG patients were enrolled in this study. The polymorphisms in PLEKHA7 and COL11A1 were analyzed using quantitative PCR, and their associations were statistically tested with PACG at homozygous, heterozygous, dominant, and recessive genetic models. The levels of malondialdehyde (MDA), advanced glycation-end product (AOPP), protein carbonyl (PC), and ischemia modified albumin (IMA) were quantitated colorimetrically, and their associations with PACG were analyzed statistically. The associations of MDA, AOPP, PC, and IMA with elevated intraocular pressure (IOP) were statistically tested.
Neither significant difference in the genotype distribution nor allele frequency of PLEKHA7 11024102 T>C (p = 0.425 and 0.517, respectively) and COL11A1 rs3753841 G>A (p = 0.600 and 0.473, respectively) were recorded under any of the tested genetic models. Either rs11024102 PLEKHA7 or rs3753841 COL11A1 was not significantly (p > 0.025 after Bonferroni correction) associated with an increased risk of PACG in Egyptians. Egyptian patients with PACG showed significant elevations in the serum levels of MDA, AOPP, and PC either in patients with or without cases with diabetes mellites, hypertension, coronary vascular diseases, and smoking. Serum levels of MDA, AOPP, and PC were significantly associated with PACG in Egyptians (p < 0.013 after Bonferroni correction). However, MDA and PC only showed significant associations with the elevation in the IOP (p = 0.007 and 0.045, respectively) in PACG patients.
Both rs11024102 and rs3753841 could not be considered as potential gene-dependent risk factors for PACG pathogenesis in Egyptians. On the other hand, serum levels of MDA, AOPP, and PC might be considered risk factors for PACG. Moreover, MDA and PC could serve as good predictors for the elevation of the IOP in PACG disease.
原发性闭角型青光眼（PACG）是中东地区主要的致盲原因之一，遗传位点和全身氧化应激是潜在的风险因素。当前的病例对照研究旨在调查埃及患者中含普列克底物蛋白同源结构域家族A成员7（PLEKHA7）中的rs11024102、胶原11 A1（COL11A1）中的rs3753841以及全身氧化应激标志物与PACG的关联。本研究纳入了35名对照受试者和64名PACG患者。使用定量PCR分析PLEKHA7和COL11A1中的多态性，并在纯合子、杂合子、显性和隐性遗传模型下对它们与PACG的关联进行统计学检验。采用比色法测定丙二醛（MDA）、晚期糖基化终产物（AOPP）、蛋白质羰基（PC）和缺血修饰白蛋白（IMA）的水平，并对它们与PACG的关联进行统计学分析。对MDA、AOPP、PC和IMA与眼压升高（IOP）的关联进行统计学检验。
在任何测试的遗传模型下，均未记录到PLEKHA7 11024102 T>C（分别为p = 0.425和0.517）和COL11A1 rs3753841 G>A（分别为p = 0.600和0.473）的基因型分布或等位基因频率存在显著差异。在埃及人中，rs11024102 PLEKHA7或rs3753841 COL11A1与PACG风险增加均无显著关联（经Bonferroni校正后p>0.025）。患有或未患有糖尿病、高血压、冠状动脉血管疾病和吸烟的埃及PACG患者血清中MDA、AOPP和PC水平均显著升高。埃及人中，血清MDA、AOPP和PC水平与PACG显著相关（经Bonferroni校正后p<0.013）。然而，在PACG患者中，只有MDA和PC与IOP升高显著相关（分别为p = 0.007和0.045）。
在埃及人中，rs11024102和rs3753841均不能被视为PACG发病机制中潜在的基因依赖性风险因素。另一方面，血清MDA、AOPP和PC水平可能被视为PACG的风险因素。此外，MDA和PC可作为PACG疾病中IOP升高的良好预测指标。
