Clinical phenotypes associated with the complement factor H Y402H variant in age-related macular degeneration.
OBJECTIVE
To determine whether the complement factor H (CFH) Y402H variant is associated with specific age-related macular degeneration (AMD) clinical phenotypes.


METHODS
Retrospective, case-control study.


METHODS
One hundred and eighty-eight white subjects with AMD and 189 control subjects were genotyped for the T-to-C polymorphism in exon 9 of the CFH gene by restriction-fragment length analysis and deoxyribonucleic acid (DNA) sequencing using genomic DNA from mouthwash samples. AMD phenotypes were characterized by clinical examination, fundus photography, and fluorescein angiography.


RESULTS
Heterozygosity for the at-risk genotype (TC) increased the likelihood for AMD 2.1-fold (95% confidence interval [CI], 1.3 to 3.3), whereas homozygosity for the genotype (CC) increased the likelihood for AMD 6.5-fold (95% CI, 3.4 to 12.5) in our population. The C allele was associated significantly with predominantly classic choroidal neovascularization (odds ratio [OR], 2.01; 95% CI, 1.34 to 3.30). Neovascular lesion size was similar among the three genotypes (P = .67).


CONCLUSIONS
The Y402H CFH variant carried a significantly increased risk for developing AMD in our population. Genotype and phenotype correlations regarding choroidal neovascular lesion type were observed.
Brantley
Milam A
MA
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, Missouri 63110, USA. brantley@vision.wustl.edu
Edelstein
Sean L
SL
King
Jennifer M
JM
Apte
Rajendra S
RS
Kymes
Steven M
SM
Shiels
Alan
A
D000368:Aged; D016022:Case-Control Studies; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA
C493495:CFH protein, human; D017242:Complement Factor H