Three major loci involved in age-related macular degeneration are also associated with polypoidal choroidal vasculopathy.
OBJECTIVE
To investigate the frequency of variants in 3 major age-related macular degeneration (AMD)-associated loci in patients of European-American descent with polypoidal choroidal vasculopathy (PCV).


METHODS
Cross-sectional, case-control association study.


METHODS
Fifty-five patients with PCV, 368 patients with advanced AMD, and 368 age-matched and ethnically matched unaffected controls of European-American descent.


METHODS
Association analysis of allele and genotype frequencies, determined by TaqMan assays, was performed for the following haplotype-tagging single nucleotide polymorphisms (htSNPs): risk alleles in the complement factor H (CFH) gene (Y402H and IVS14) in the ARMS2/HTRA1 locus on 10q26 (A69S) and protective alleles in CFH (IVS1 and IVS6) and in the complement factor B/complement component C2 (CFB/C2) locus (IVS10 and H9L).


METHODS
Allele and genotype frequencies of the htSNPs in the CFH, CFB/C2, and ARMS2/HTRA1 loci.


RESULTS
Four AMD-associated haplotype-tagging alleles (rs547154, rs1061170, rs1410996, rs10490924) in the 3 major loci, CFH, CFB/C2, and ARMS2/HTRA1, also were statistically significantly associated with the PCV phenotype (P<0.05). Three other alleles from the same loci (rs4151667, rs529825, rs3766404) showed a trend toward association (P<0.2) but did not reach statistical significance, possibly because of the combined effects of a relatively small sample size and low minor allele frequency in the screened populations.


CONCLUSIONS
The PCV phenotype in Caucasian patients is associated with the major alleles/genotypes in the AMD-associated loci, suggesting that PCV and AMD are genetically similar in the tested loci.
Lima
Luiz H
LH
The Vitreous, Retina, Macula Consultants of New York and the LuEsther T. Mertz Retina Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, USA.
Schubert
Carl
C
Ferrara
Daniela C
DC
Merriam
Joanna E
JE
Imamura
Yutaka
Y
Freund
K Bailey
KB
Spaide
Richard F
RF
Yannuzzi
Lawrence A
LA
Allikmets
Rando
R
D000368:Aged; D016022:Case-Control Studies; D002829:Choroid / Q000098:blood supply*; D015862:Choroid Diseases / Q000175:diagnosis / Q000235:genetics*; D003175:Complement C2 / Q000235:genetics; D011415:Complement Factor B / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D003165:Complement System Proteins / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D005451:Fluorescein Angiography; D020869:Gene Expression Profiling; D005787:Gene Frequency; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D007208:Indocyanine Green; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D016491:Peripheral Vascular Diseases / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics; D044465:White People / Q000235:genetics
C514392:ARMS2 protein, human; C493495:CFH protein, human; D003175:Complement C2; D011506:Proteins; D017242:Complement Factor H; D003165:Complement System Proteins; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases; D011415:Complement Factor B; D007208:Indocyanine Green