Gene–Gene Interactions of CFH and LOC387715/ARMS2 with Korean Exudative Age-related Macular Degeneration Patients

Abstract

Purpose: To evaluate the association and interaction of single nucleotide polymorphisms in CFH and LOC387715/ARMS2 with age-related macular degeneration (AMD) in a Korean population.

Methods: A total of 114 exudative AMD patients and 240 normal subjects participated in the study. PCR and direct sequencing were used to screen SNPs in the CFH and in the LOC387715/ARMS2. Genotype and haplotype analyses were performed. Two-locus gene–gene interactions were evaluated by the data mining approach multifactor-dimensionality reduction method.

Results: The *C/*T genotype frequency of rs1061170 in CFH showed a significant difference (OR = 1.79). Genotype and allele frequencies of rs551397 (*C/*C, OR = 2.84; *C, OR = 1.67) and rs800292 (*G/*G, OR = 2.198; *G, OR = 1.676) in CFH, and rs10490924 (T/*T, OR = 12.45; *T, OR = 4.45) and rs2736911 (*C/*C, OR = 3.21; *C, OR = 2.71) in LOC387715/ARMS2 were significantly higher in patients. In the haplotype analysis, C-T of rs2736911-rs10490924 in LOC387715/ARMS2 (OR = 4.85) and C-G of rs551397-rs800292 in CFH (OR = 2.22) predisposed significantly to AMD. After cross-validation consistency (CVC) and permutation tests, we identified the 1 marker model (rs10490924), which has a prediction accuracy of 73.5%, and the two locus model, rs10490924_ rs800292, with 75.3% balanced accuracy in predicting AMD disease risk.

Conclusions: Korean individuals with the LOC387715/ARMS2 rs10490924, and to a lesser extent, CFH rs800292 variants might be at a greater risk for the development of exudative AMD. Furthermore, the risk of exudative AMD may increase significantly if these variants are both present in the two genes.

• age-related macular degeneration
• association
• complement factor H
• LOC387715/ARMS2
• haplotype
• multifactor-dimensionality reduction method
• single nucleotide polymorphisms

Acknowledgements

We thank the Korea Eye Tissue and Gene Bank, The Catholic University of Korea and the staff of the Department of Ophthalmology, St. Mary’s Hospital, Seoul, Korea.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported by the Catholic Medical Center Research Foundation (Program year of 2007).