Yuyu Chou1,2, Zixi Sun1,2, Ye Wang3, Yuhan Wang4, Jin Ma1,2, Dianxi Zhang5, Yong Zhong6,7. 1. Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China. 2. Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences, Beijing, 100730, China. 3. School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. 4. Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China. 5. Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College & China Academy of Medical Science, Beijing, China. 6. Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China. zhongy_pumch@126.com. 7. Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences, Beijing, 100730, China. zhongy_pumch@126.com.
Abstract
PURPOSE: To elucidate the potential role of genetic polymorphisms of apolipoprotein E (APOE) in nonarteritic anterior ischemic optic neuropathy (NAION) and the association between APOE and NAION-induced ocular impairments. METHODS: A total of 73 NAION patients and 73 sex- and age-matched healthy controls were recruited for the study. Genomic DNA was isolated from peripheral blood samples. The alleles and genotypes of APOE were explored. The interaction between APOE and medical comorbidities was assessed by the multifactor dimensionality reduction (MDR) method. Among 81 affected eyes of NAION patients, an additional association study of APOE isoforms with visual impairments was carried out. RESULTS: The allele and genotype frequencies for APOE showed significant differences when comparing NAION cases and controls. Multivariate analysis adjusted for age, sex, hypertension, dyslipidemia, diabetes mellitus, cardiovascular disease, and cerebrovascular disease revealed that the ε3/ε4 genotype (OR = 3.86, 95% CI = 1.13-13.25, p = 0.032) and ε4 allele (OR = 3.55, 95% CI = 1.05-11.99, p = 0.041) were strong independent risk factors for NAION. Compared to eyes with the ε3/ε3 + ε2/ε4 genotype, individuals with the ε4/ε4 + ε3/ε4 genotype had worse visual field defects (VFDs) and thinner macular ganglion cell complex (mGCC) thicknesses with larger focal loss of volume (FLV) and general loss of volume (GLV). Compared to ε4 noncarriers, ε4 carriers also tended to have more serious VFD and mGCC loss. CONCLUSIONS: APOE polymorphisms conferred a significant risk of NAION and were significantly related to ocular impairments caused by NAION.
PURPOSE: To elucidate the potential role of genetic polymorphisms of apolipoprotein E (APOE) in nonarteritic anterior ischemic optic neuropathy (NAION) and the association between APOE and NAION-induced ocular impairments. METHODS: A total of 73 NAION patients and 73 sex- and age-matched healthy controls were recruited for the study. Genomic DNA was isolated from peripheral blood samples. The alleles and genotypes of APOE were explored. The interaction between APOE and medical comorbidities was assessed by the multifactor dimensionality reduction (MDR) method. Among 81 affected eyes of NAION patients, an additional association study of APOE isoforms with visual impairments was carried out. RESULTS: The allele and genotype frequencies for APOE showed significant differences when comparing NAION cases and controls. Multivariate analysis adjusted for age, sex, hypertension, dyslipidemia, diabetes mellitus, cardiovascular disease, and cerebrovascular disease revealed that the ε3/ε4 genotype (OR = 3.86, 95% CI = 1.13-13.25, p = 0.032) and ε4 allele (OR = 3.55, 95% CI = 1.05-11.99, p = 0.041) were strong independent risk factors for NAION. Compared to eyes with the ε3/ε3 + ε2/ε4 genotype, individuals with the ε4/ε4 + ε3/ε4 genotype had worse visual field defects (VFDs) and thinner macular ganglion cell complex (mGCC) thicknesses with larger focal loss of volume (FLV) and general loss of volume (GLV). Compared to ε4 noncarriers, ε4 carriers also tended to have more serious VFD and mGCC loss. CONCLUSIONS: APOE polymorphisms conferred a significant risk of NAION and were significantly related to ocular impairments caused by NAION.
Authors: Dean M Cestari; Eric D Gaier; Peggy Bouzika; Taylor S Blachley; Lindsey B De Lott; Joseph F Rizzo; Janey L Wiggs; Jae H Kang; Louis R Pasquale; Joshua D Stein Journal: Ophthalmology Date: 2016-09-19 Impact factor: 12.079