Associations between OPA1, MFN1, and MFN2 polymorphisms and primary open angle glaucoma in Polish participants of European ancestry

Background Glaucomatous optic nerve damage is caused by selective death of retinal ganglion cells (RGCs). Another condition with underlying loss of RGCs is autosomal dominant optic atrophy (ADOA). Majority of ADOA patients have mutations in OPA1, gene responsible for mitochondrial fusion final steps. Clinical resemblance between the two diseases make genes involved in mitochondrial fusion good candidates as glaucoma genes. In this study, we investigated if selected polymorphisms of OPA1, MFN1, and MFN2 were associated with glaucoma in Polish population. Methods Four OPA1 (rs166850, rs10451941, rs7624750, rs9851685), one MFN1 (rs2111534), and two MFN2 (rs873458, rs2295281) single nucleotide polymorphisms were investigated in 304 primary open angle glaucoma patients (204 with normal tension glaucoma, 100 with high-tension glaucoma) and 258 control subjects using RT-PCR method. Results There was a significant difference in genotype frequencies of rs9851685 and rs2111534 polymorphisms between glaucoma patients and control subjects. Several genotype combinations comprising SNPs at OPA1 and MFN1 were significantly differently distributed in a three-way comparison between controls, patients with NTG and patients with HTG. None of the studied MFN2 polymorphisms was significantly associated with HTG or NTG. Conclusions In studied population, genotype CC and allele C of rs9851685 OPA1 polymorphism are NTG risk factors, whereas TT genotype and T allele of this polymorphism are protective factors against NTG. Genotype GA of rs2111534 MFN1 polymorphism is an HTG risk factor and AA genotype of this polymorphism is a protective factor against HTG. Several OPA1 and MFN2 genotype combinations are significantly associated with either increased or decreased risk of glaucoma in this population.