Y402H complement factor H polymorphism associated with exudative age-related macular degeneration in the French population.
OBJECTIVE
Identification of genetic factors for age-related macular degeneration (AMD) is of crucial importance in this common cause of blindness. A positive association between Y402H polymorphism of the complement factor H (CFH) gene and AMD has been recently reported in North American populations but not yet in European populations. The exudative form of AMD is rapidly progressive and usually associated with a severe prognosis. Our purpose was to investigate this association in a French population specifically affected with exudative AMD, in a case-control study.


METHODS
Two series of unrelated exudative AMD patients, sporadic cases (n=60, mean age 74.9+/-5.7) and familial cases (n=81, mean age 74.0+/-9.4) were compared with healthy controls (n=91, mean age 74.6+/-6.3). The coding region of exon 9 of CFH was examined for the Y402H polymorphism by PCR-direct sequencing.


RESULTS
The 1,279-C allele frequencies were significantly higher in exudative AMD patients than controls (0.564 compared to 0.302; p<0.0001). Genotypic distribution of the Y402H polymorphism was significantly different between sporadic cases compared to controls (chi2=14.48 with 2 df, p<0.0007) and between familial cases compared to controls (chi2=23.78 with 2 df, p<0.0001). The odds ratio (OR) for exudative AMD was 3.00 CI95% (1.60-5.62) for heterozygotes (CT) and 6.93 CI95% (3.11-15.46) for homozygotes (CC).


CONCLUSIONS
These results suggest the contribution of the Y402H polymorphism of the CFH gene to exudative AMD susceptibility also in the French population. This relationship with the CFH may lead to early detection and new strategies for prevention and treatment of AMD.
Souied
Eric H
EH
Creteil University Eye Clinic, Faculte de Medecine Henri Mondor, Creteil, France. eric.souied@chicreteil.fr
Leveziel
Nicolas
N
Richard
Florence
F
Dragon-Durey
Marie-Agnès
MA
Coscas
Gabriel
G
Soubrane
Gisèle
G
Benlian
Pascale
P
Fremeaux-Bacchi
Veronique
V
D000368:Aged; D017242:Complement Factor H / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005122:Exudates and Transudates; D005260:Female; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D006801:Humans; D008268:Macular Degeneration / Q000208:ethnology / Q000235:genetics*; D008297:Male; D009154:Mutation; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D044465:White People
C493495:CFH protein, human; D017242:Complement Factor H