Atanasovska Velkovska Makedonka, Goričar Katja, Blagus Tanja, Dolžan Vita, Cvenkel Barbara
Department of Ophthalmology, University Medical Centre Ljubljana, Grablovičeva 46, 1000 Ljubljana, Slovenia.
Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
Int J Mol Sci. 2024 Dec 16;25(24):13464. doi: 10.3390/ijms252413464.
In open-angle glaucoma, the increase in intraocular pressure (IOP) is caused by an increased resistance to aqueous humour outflow in the trabecular meshwork. Since genetic variability of matrix metalloproteinase (MMP) genes may influence extracellular matrix remodelling, we investigated their association with glaucoma risk and/or response to treatment. The retrospective part of the study included patients with primary open-angle glaucoma and ocular hypertension (OHT); in the prospective part of the study, newly diagnosed patients with POAG or OHT were randomised to receive either latanoprost or selective laser trabeculoplasty (SLT) as the initial treatment. The reduction in IOP was measured 6 weeks after treatment. The following MMP single nucleotide polymorphisms were genotyped: rs243865, rs243849, and rs7201; rs3025058; rs17576, rs17577, rs20544, and rs2250889; rs1042704, rs1042704, and rs743257. Logistic regression was used to calculate odds ratios to assess the association between MMP polymorphism and risk of POAG or OHT, glaucoma phenotypes and response to treatment. Only carriers of the rs3025058 TT genotype had a significantly higher risk of OHT, more advanced glaucoma, and a higher C/D ratio in the additive and dominant models. None of the investigated MMP polymorphisms were associated with response to treatment with latanoprost and SLT in our study population.
在开角型青光眼中,眼内压(IOP)升高是由小梁网中房水流出阻力增加所致。由于基质金属蛋白酶(MMP)基因的遗传变异性可能影响细胞外基质重塑,我们研究了它们与青光眼风险和/或治疗反应的关联。该研究的回顾性部分纳入了原发性开角型青光眼和高眼压症(OHT)患者;在研究的前瞻性部分,新诊断的原发性开角型青光眼或高眼压症患者被随机分配接受拉坦前列素或选择性激光小梁成形术(SLT)作为初始治疗。治疗6周后测量眼压降低情况。对以下MMP单核苷酸多态性进行基因分型:rs243865、rs243849和rs7201;rs3025058;rs17576、rs17577、rs20544和rs2250889;rs1042704、rs1042704和rs743257。采用逻辑回归计算比值比,以评估MMP多态性与原发性开角型青光眼或高眼压症风险、青光眼表型及治疗反应之间的关联。在加性和显性模型中,只有rs3025058 TT基因型携带者患高眼压症的风险显著更高、青光眼更严重且杯盘比更高。在我们的研究人群中,所研究的MMP多态性均与拉坦前列素和SLT治疗反应无关。