Mortaza Bonyadi1,2, Tahereh Mohammadian1, Mohammad Hossein Jabbarpoor Bonyadi1,3, Nikou Fotouhi1, Masoud Soheilian3, Alireza Javadzadeh4, Hamidreza Moein3, Mehdi Yaseri5. 1. a Center of Excellence for Biodiversity, Faculty of Natural Sciences , University of Tabriz , Tabriz , Iran. 2. b Liver and Gastrointestinal Disease Research Center , Tabriz University of Medical Sciences , Tabriz , Iran. 3. c Ocular Tissue Engineering Research Center, Ophthalmic Research Center , Shahid Beheshti University of Medical Sciences , Tehran , Iran. 4. d Department of Ophthalmology , Tabriz University of Medical Sciences , Tabriz , Iran. 5. e Department of Biostatistics and Epidemiology , Tehran University of Medical Sciences , Tehran , Iran.
Abstract
BACKGROUND: Age related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population. Inflammatory mediators play an important role in AMD pathogenesis and immune-related gene polymorphisms are shown to increase the risk. Complement system is an important mediator of the immunity system and several genes encoding proteins involved in this system are associated with susceptibility to AMD. The central element of the complement cascade, C3 has been a plausible candidate since its cleavage product C3a was found in drusen. This study was planned to evaluate the association of C3-rs2230199 (R102G) variants with advanced type AMD in this cohort. MATERIALS AND METHODS: In this case-control study, 494 participants consisting of 266 AMD patients (187 wet AMD and 79 advanced dry AMD) and 228 samples from unrelated healthy controls were enrolled for evaluation. Extracted-DNA samples were amplified to obtain fragments including the polymorphic region. RESULTS: The distribution of the R102G genotypes was significantly different in the AMD patients compared to controls (p = 0.001).The Odds Ratio compared to CC individuals was 1.69 (95% CI 1.15-2.49) for GC individuals and 6.48 (95% CI1.87-22.43) for GG individuals. The Odds Ratio compared to the C allele was 2.31 (95% CI 0.48-11) for the G allele. GG and GC genotypes and G allele were significantly associated with both types of advanced-AMD. Individuals carrying GG genotype have over a six-fold risk of developing AMD in comparison to those carrying the CC genotype in this cohort. Our meta-analysis pooled data showed that our homozygous individuals for GG have a higher risk of AMD compared to previous publications in different nations (p = 0.017). CONCLUSIONS: Our study shows C3 to be a relatively strong susceptibility gene for advanced-type-AMD (exudative-and-geographic-atrophy) in an Iranian population.
BACKGROUND: Age related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population. Inflammatory mediators play an important role in AMD pathogenesis and immune-related gene polymorphisms are shown to increase the risk. Complement system is an important mediator of the immunity system and several genes encoding proteins involved in this system are associated with susceptibility to AMD. The central element of the complement cascade, C3 has been a plausible candidate since its cleavage product C3a was found in drusen. This study was planned to evaluate the association of C3-rs2230199 (R102G) variants with advanced type AMD in this cohort. MATERIALS AND METHODS: In this case-control study, 494 participants consisting of 266 AMDpatients (187 wet AMD and 79 advanced dry AMD) and 228 samples from unrelated healthy controls were enrolled for evaluation. Extracted-DNA samples were amplified to obtain fragments including the polymorphic region. RESULTS: The distribution of the R102G genotypes was significantly different in the AMDpatients compared to controls (p = 0.001).The Odds Ratio compared to CC individuals was 1.69 (95% CI 1.15-2.49) for GC individuals and 6.48 (95% CI1.87-22.43) for GG individuals. The Odds Ratio compared to the C allele was 2.31 (95% CI 0.48-11) for the G allele. GG and GC genotypes and G allele were significantly associated with both types of advanced-AMD. Individuals carrying GG genotype have over a six-fold risk of developing AMD in comparison to those carrying the CC genotype in this cohort. Our meta-analysis pooled data showed that our homozygous individuals for GG have a higher risk of AMD compared to previous publications in different nations (p = 0.017). CONCLUSIONS: Our study shows C3 to be a relatively strong susceptibility gene for advanced-type-AMD (exudative-and-geographic-atrophy) in an Iranian population.