Association between COL4A2 gene polymorphisms and nonarteritic anterior ischemic optic neuropathy

Objectives: The aim of this study is to elucidate the potential role of COL4A2 gene polymorphisms in nonarteritic ischemic optic neuropathy (NAION) and to investigate the relationship between NAION-related ocular pathologies. Additionally, this study aims to contribute to the understanding of the pathophysiology by evaluating the association between cerebral small vessel diseases, lacunar infarctions and NAION. Materials and Methods: A total of 51 NAION patients and 57 age- and gender-matched healthy controls were included in the study. Participants underwent routine ophthalmological examination and optical coherence tomography imaging. Genomic DNA was isolated from peripheral blood samples. The alleles and genotypes of four single nucleotide polymorphisms (SNPs) of COL4A2 were amplified using polymerase chain reaction (PCR). Logistic regression analysis was used to evaluate the relationship between COL4A2 and NAION, as well as ocular pathologies. Patients who had not undergone imaging in the last 6 months underwent cranial magnetic resonance imaging (MRI) to investigate the presence of cerebral small vessel disease findings and lacunar infarctions in the NAION group. Results: The study included 51 NAION patients and 57 healthy individuals. The patient group exhibited significantly higher rates of diabetes mellitus (DM), hypertension, hyperlipidemia, and cardiovascular disease history compared to the control group (p=0.002, p<0.001, p<0.001, p<0.001, respectively). There were no significant differences between the groups regarding cerebrovascular disease and sleep apnea syndrome history. COL4A2 rs76425569 allele and genotype frequencies showed significant differences between NAION cases and controls (p=0.003). After adjusting for confounding variables, individuals with the AA genotype of the rs76425569 polymorphism were found to have a higher likelihood of developing NAION compared to those with the GG genotype (OR=2.451, 95% CI 1.086-5.659, p=0.033). There was no statistically significant difference between COL4A2 polymorphism genotypes and cerebral small vessel disease and lacunar infarctions. The presence of the A allele in either or both rs445348 and rs76425569 gene polymorphisms increased the risk of NAION by 5.6 times compared to those without the alleles (OR=5.6, 95% CI 1.212-40.181, p=0.043). NAION eyes carrying the AA genotype in at least one of the two gene polymorphism regions had better ganglion cell volume and final visual acuity compared to non-carriers (p=0.046, p=0.012, respectively). Conclusion: An increase in the presence of the G/A polymorphism of the COL4A2 rs76425569 gene was observed in NAION patients. We believe that the AA genotype could be a significant risk factor for the development of NAION in our population. Our data suggest that the presence of the AA genotype in the rs76425569 and rs445348 gene polymorphisms may increase the risk of NAION while potentially leading to a milder clinical presentation. This study is the first to demonstrate the potential involvement of the COL4A2 gene in NAION pathogenesis. Keywords: COL4A2, Nonarteritic ischemic optic neuropathy, Gene polymorphism, Lacunar infarction, Cerebral small vessel disease ASSOCIATION BETWEEN COL4A2 GENE POLYMORPHISMS AND NONARTERITIC ANTERIOR ISCHEMIC OPTIC NEUROPATHY ABSTRACT Objectives: The aim of this study is to elucidate the potential role of COL4A2 gene polymorphisms in nonarteritic ischemic optic neuropathy (NAION) and to investigate the relationship between NAION-related ocular pathologies. Additionally, this study aims to contribute to the understanding of the pathophysiology by evaluating the association between cerebral small vessel diseases, lacunar infarctions and NAION. Materials and Methods: A total of 51 NAION patients and 57 age- and gender-matched healthy controls were included in the study. Participants underwent routine ophthalmological examination and optical coherence tomography imaging. Genomic DNA was isolated from peripheral blood samples. The alleles and genotypes of four single nucleotide polymorphisms (SNPs) of COL4A2 were amplified using polymerase chain reaction (PCR). Logistic regression analysis was used to evaluate the relationship between COL4A2 and NAION, as well as ocular pathologies. Patients who had not undergone imaging in the last 6 months underwent cranial magnetic resonance imaging (MRI) to investigate the presence of cerebral small vessel disease findings and lacunar infarctions in the NAION group. Results: The study included 51 NAION patients and 57 healthy individuals. The patient group exhibited significantly higher rates of diabetes mellitus (DM), hypertension, hyperlipidemia, and cardiovascular disease history compared to the control group (p=0.002, p<0.001, p<0.001, p<0.001, respectively). There were no significant differences between the groups regarding cerebrovascular disease and sleep apnea syndrome history. COL4A2 rs76425569 allele and genotype frequencies showed significant differences between NAION cases and controls (p=0.003). After adjusting for confounding variables, individuals with the AA genotype of the rs76425569 polymorphism were found to have a higher likelihood of developing NAION compared to those with the GG genotype (OR=2.451, 95% CI 1.086-5.659, p=0.033). There was no statistically significant difference between COL4A2 polymorphism genotypes and cerebral small vessel disease and lacunar infarctions. The presence of the A allele in either or both rs445348 and rs76425569 gene polymorphisms increased the risk of NAION by 5.6 times compared to those without the alleles (OR=5.6, 95% CI 1.212-40.181, p=0.043). NAION eyes carrying the AA genotype in at least one of the two gene polymorphism regions had better ganglion cell volume and final visual acuity compared to non-carriers (p=0.046, p=0.012, respectively). Conclusion: An increase in the presence of the G/A polymorphism of the COL4A2 rs76425569 gene was observed in NAION patients. We believe that the AA genotype could be a significant risk factor for the development of NAION in our population. Our data suggest that the presence of the AA genotype in the rs76425569 and rs445348 gene polymorphisms may increase the risk of NAION while potentially leading to a milder clinical presentation. This study is the first to demonstrate the potential involvement of the COL4A2 gene in NAION pathogenesis. Keywords: COL4A2, Nonarteritic ischemic optic neuropathy, Gene polymorphism, Lacunar infarction, Cerebral small vessel disease ASSOCIATION BETWEEN COL4A2 GENE POLYMORPHISMS AND NONARTERITIC ANTERIOR ISCHEMIC OPTIC NEUROPATHY ABSTRACT Objectives: The aim of this study is to elucidate the potential role of COL4A2 gene polymorphisms in nonarteritic ischemic optic neuropathy (NAION) and to investigate the relationship between NAION-related ocular pathologies. Additionally, this study aims to contribute to the understanding of the pathophysiology by evaluating the association between cerebral small vessel diseases, lacunar infarctions and NAION. Materials and Methods: A total of 51 NAION patients and 57 age- and gender-matched healthy controls were included in the study. Participants underwent routine ophthalmological examination and optical coherence tomography imaging. Genomic DNA was isolated from peripheral blood samples. The alleles and genotypes of four single nucleotide polymorphisms (SNPs) of COL4A2 were amplified using polymerase chain reaction (PCR). Logistic regression analysis was used to evaluate the relationship between COL4A2 and NAION, as well as ocular pathologies. Patients who had not undergone imaging in the last 6 months underwent cranial magnetic resonance imaging (MRI) to investigate the presence of cerebral small vessel disease findings and lacunar infarctions in the NAION group. Results: The study included 51 NAION patients and 57 healthy individuals. The patient group exhibited significantly higher rates of diabetes mellitus (DM), hypertension, hyperlipidemia, and cardiovascular disease history compared to the control group (p=0.002, p<0.001, p<0.001, p<0.001, respectively). There were no significant differences between the groups regarding cerebrovascular disease and sleep apnea syndrome history. COL4A2 rs76425569 allele and genotype frequencies showed significant differences between NAION cases and controls (p=0.003). After adjusting for confounding variables, individuals with the AA genotype of the rs76425569 polymorphism were found to have a higher likelihood of developing NAION compared to those with the GG genotype (OR=2.451, 95% CI 1.086-5.659, p=0.033). There was no statistically significant difference between COL4A2 polymorphism genotypes and cerebral small vessel disease and lacunar infarctions. The presence of the A allele in either or both rs445348 and rs76425569 gene polymorphisms increased the risk of NAION by 5.6 times compared to those without the alleles (OR=5.6, 95% CI 1.212-40.181, p=0.043). NAION eyes carrying the AA genotype in at least one of the two gene polymorphism regions had better ganglion cell volume and final visual acuity compared to non-carriers (p=0.046, p=0.012, respectively). Conclusion: An increase in the presence of the G/A polymorphism of the COL4A2 rs76425569 gene was observed in NAION patients. We believe that the AA genotype could be a significant risk factor for the development of NAION in our population. Our data suggest that the presence of the AA genotype in the rs76425569 and rs445348 gene polymorphisms may increase the risk of NAION while potentially leading to a milder clinical presentation. This study is the first to demonstrate the potential involvement of the COL4A2 gene in NAION pathogenesis. Keywords: COL4A2, Nonarteritic ischemic optic neuropathy, Gene polymorphism, Lacunar infarction, Cerebral small vessel disease