Genotype-phenotype correlations for exudative Age-related Macular Degeneration associated with homozygous HTRA1 and CFH genotypes
Nicolas Leveziel 1,
Jennyfer Zerbib 1,
Florence RICHARD 2,
giuseppe querques 1,
Gilles Morineau 3,
Veronique FREMEAUX-BACCHI 4,
Gabriel Coscas 1,
Gisele Soubrane 1,
Pascale BENLIAN 3,
and
Eric H. Souied 5*
1 Ophthalmology, Creteil Eye Clinic of University Paris 12, Creteil, France
2 INSERM UMR744, Institut Pasteur de Lille, Universite lille 2, lille, France
3 UMRS 538, CHU Saint Antoine, INSERM, paris, France
4 Service d'Immunologie Biologique, Hopital Europeen Georges Pompidou, paris, France
5 Ophthalmology, Creteil Eye Clinic of University Paris 12, 40, avenue de verdun, Creteil, 94000, France
* To whom correspondence should be addressed. E-mail: eric.souied{at}chicreteil.fr.
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Abstract |
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Purpose: Major genetic factors for age-related macular degeneration (AMD) have
recently been identified as susceptibility risk factors, including polymorphisms of
HTRA1 and CFH genes. Our purpose was to analyze the angiographic features of
patients harbouring homozygous genotypes for HTRA1 and CFH genes in a French
exudative AMD population.
Patients and Methods: 200 patients affected with exudative AMD were genotyped
for the polymorphisms rs11200638 of HTRA1 gene and rs10611710 of 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 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% of RAP. Group 2 (n=12) presented 50.0% classic and PC, 33.3% occult
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 % of classic and PC,
52.9% of occult, 11.8% of MC and 5.9% of RAP. Occult CNV or MC CNV were 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 group 3 (50% versus
10.7%; p<0.03).
Conclusions: This attempt for a genotypic-angiographic correlation in exudative
AMD population suggests an association between occult or MC CNV and the CFH
polymorphism and between classic and PC CNV and the HTRA1 polymorphism.
Key Words:
age-related macular degeneration, candidate genes, fluorescein angiography
