Genotype-phenotype correlations for exudative age-related macular degeneration associated with homozygous HTRA1 and CFH genotypes.
OBJECTIVE
Major genetic factors for age-related macular degeneration (AMD) have recently been identified as susceptibility risk factors, including polymorphisms of HTRA1 and CFH genes. The purpose was to analyze the angiographic features of patients harboring homozygous genotypes for HTRA1 and CFH genes in a French exudative AMD population.


METHODS
Two hundred patients affected with exudative AMD were genotyped for the polymorphisms rs11200638 of the HTRA1 gene and rs10611710 of the CFH gene. Four homozygous groups were extracted from the entire cohort: double homozygous for wild-type alleles of both genes (group 1), homozygous for the polymorphism of the HTRA1 gene only (group 2), homozygous for the polymorphism of the CFH gene only (group 3), and double homozygous carriers for both polymorphisms (group 4). Choroidal neovascularization (CNV) was graded as classic and predominantly classic (PC), occult, minimally classic (MC), or retinal angiomatosis proliferation (RAP).


RESULTS
Group 1 (n = 9) presented 44.4% classic and PC, 33.3% occult, 11.1% MC, and 11.1% RAP. Group 2 (n = 12) presented 50.0% classic and PC, 33.3% occult, no MC CNV and 16.7% RAP. Group 3 (n = 28) presented 10.7% classic and PC, 67.9% occult, 14.3% MC, and 7.1% RAP. Group 4 (n = 17) presented 29.4% classic and PC, 52.9% occult, 11.8% MC, and 5.9% RAP. Occult CNV or MC CNV was more frequently observed in group 3 than in group 2 (82.1% vs 33.3%; P < 0.02). Classic and PC CNV were more frequently observed in group 2 than in group 3 (50% vs. 10.7%; P < 0.03).


CONCLUSIONS
This attempt at a genotypic-angiographic correlation in an exudative AMD sample suggests an association between occult or MC CNV and the CFH polymorphism and between classic and PC CNV and the HTRA1 polymorphism.
Leveziel
Nicolas
N
Faculte de Medecine Henri Mondor, Creteil University Eye Clinic, Creteil, France.
Zerbib
Jennyfer
J
Richard
Florence
F
Querques
Giuseppe
G
Morineau
Gilles
G
Fremeaux-Bacchi
Veronique
V
Coscas
Gabriel
G
Soubrane
Gisèle
G
Benlian
Pascale
P
Souied
Eric H
EH
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000792:Angiography; D000798:Angiomatosis / Q000000981:diagnostic imaging / Q000209:etiology; D020256:Choroidal Neovascularization / Q000145:classification / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics; D015331:Cohort Studies; D017242:Complement Factor H / Q000235:genetics; D005122:Exudates and Transudates / Q000378:metabolism*; D005260:Female; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006720:Homozygote; D006801:Humans; D008268:Macular Degeneration / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D012171:Retinal Vessels / Q000000981:diagnostic imaging; D012697:Serine Endopeptidases / Q000235:genetics*
C493495:CFH protein, human; D017242:Complement Factor H; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases