Comprehensive analysis of complement factor H and LOC387715/ARMS2/HTRA1 variants with respect to phenotype in advanced age-related macular degeneration.
OBJECTIVE
To examine the interaction of genotypic variation of 16 single-nucleotide polymorphisms (SNP) in the complement factor H (CFH) and LOC387715/ARMS2/HTRA1 loci with clinical characteristics of age-related macular degeneration (AMD).


METHODS
Retrospective cohort study.


METHODS
Eighty-four patients with neovascular AMD were genotyped using direct sequencing or Sequenom iPLEX technology. The Fisher exact test, Cochran-Mantel-Haenszel statistics, and Mann-Whitney U test were used to assess the effect of each SNP with respect to the following phenotypic manifestations: age at diagnosis, gender, affected eye, study and fellow eye visual acuity at diagnosis and at last follow-up, study eye best acuity during follow-up, presence of large drusen and retinal pigment epithelium (RPE) hyperpigmentation in study and fellow eye, choroidal neovascularization (CNV) angiographic subtype (classic vs occult), CNV size, presence of wet AMD in fellow eye, presence of dry AMD in fellow eye, and smoking history.


RESULTS
Only SNPs in the LOC387715/ARMS2/HTRA1 (10q26) region were associated with disease phenotypes. The polymorphisms rs10664316 and rs1049331 were associated with a decreased risk of poor visual acuity during follow-up and at diagnosis; rs2672598 and rs2293870 were associated with a decreased risk of RPE hyperpigmentation; rs10664316 was associated with a decreased risk of RPE hyperpigmentation with large drusen in the study eye, but an increased risk of large drusen in the fellow eye; rs11200638 was associated with an increased risk of larger CNV; rs10490924 and rs11200638 were associated with younger age of diagnosis.


CONCLUSIONS
Several polymorphisms examined in the LOC387715/ARMS2/HTRA1 locus, but none in the CFH region, correlated with specific phenotypic attributes of AMD.
Ocular Molecular Genetics Institute, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, USA.
Michael T
MT
Andreoli
Margaux A
MA
Morrison
Ben J
BJ
Kim
Ling
L
Chen
Scott M
SM
Adams
Joan W
JW
Miller
Margaret M
MM
DeAngelis
Ivana K
IK
Kim
D000368:Aged; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000235:genetics*; D014792:Visual Acuity
C514392:ARMS2 protein, human; C493495:CFH protein, human; D011506:Proteins; D017242:Complement Factor H; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases