Evaluation of CC-cytokine ligand 2 and complementary factor H Y402H polymorphisms and their interactional association with age-related macular degeneration.
OBJECTIVE
To evaluate the association of CC-cytokine ligand 2 CCL2-2518 (rs1024611) single nucleotide polymorphism, complement factor H (CFH Y402H) and their possible interaction in developing advanced age-related macular degeneration (AMD).


METHODS
In this case-control study, DNA samples from 266 patients with advanced AMD and 229 healthy controls were genotyped for CCL2 polymorphism and also 254 patients and 164 healthy controls were genotyped for CFH polymorphism. The possible associations of these polymorphisms with susceptibility to AMD independently and in different joint combinations were evaluated.


RESULTS
The genotype frequency for CFH was found to be significantly different between AMD and normal controls (31.5% versus 20.7%, OR = 3.56, p < 0.001 for CC and 52.4% versus 41.5%, OR = 2.96, p < 0.001 for CT genotype). However, no significant association between CCL2 polymorphism and AMD was observed in this cohort (OR = 1.15 and OR = 0.8, p = 0.172). Interestingly, studying the joint effects of two genotypes (TT genotype of CFH Y402H and AG genotype of CCL2-2518) showed more significant protective effect against AMD (p = 0.0001), while the risk effect of CC and CT genotypes of CFH was only visible in the presence of AA genotype of CCL2-2518 (p = 0.044 and p = 0.05).


CONCLUSIONS
Complement factor H Y402H polymorphism is strongly associated with advanced type AMD. Although this study revealed no association of CCL2-2518 with AMD, the risk effect of CFH genotypes was only visible in the presence of AA genotype of CCL2-2518. AG genotype of CCL2-2518 in combination with TT genotype of CFH Y402H showed significant protective effect against AMD.
Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.|Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Mortaza
M
Bonyadi
Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Zahra
Z
Foruzandeh
Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Tahereh
T
Mohammadian
Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Nikou
N
Fotouhi
Ocular Tissue Engineering Research Center, Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Masoud
M
Soheilian
Center of Excellence for Biodiversity, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.|Ocular Tissue Engineering Research Center, Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mohammad Hossein
MH
Jabbarpoor Bonyadi
Department of Ophthalmology, Tabriz University of Medical Sciences, Tabriz, Iran.
Alireza
A
Javadzadeh
Ocular Tissue Engineering Research Center, Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hamidreza
H
Moein
Department of Biostatistics and Epidemiology, Tehran University of Medical Sciences, Tehran, Iran.
Mehdi
M
Yaseri
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005451:Fluorescein Angiography; D005787:Gene Frequency; D060005:Genotyping Techniques; D057092:Geographic Atrophy / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D041623:Tomography, Optical Coherence; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000235:genetics*
C111835:CCL2 protein, human; C493495:CFH protein, human; D018932:Chemokine CCL2; D017242:Complement Factor H
CC-cytokine ligand 2; Iranian population; age-related macular degeneration; complement factor H (CFH Y402H) gene; monocyte chemo-attractant protein 1; single nucleotide polymorphism