Analysis of complement factor H Y402H, LOC387715, HTRA1 polymorphisms and ApoE alleles with susceptibility to age-related macular degeneration in Hungarian patients.
OBJECTIVE
Recent studies strongly support the role of genetic factors in the aetiology of age-related macular degeneration (AMD). We investigated the frequency of Tyr402His polymorphism of the complement factor H (CFH) gene, Ser69Ala polymorphism at LOC387715, rs11200638 polymorphism of the HTRA1 gene and different apolipoprotein E (ApoE) alleles in Hungarian patients with AMD in order to determine the disease risk conferred by these factors.


METHODS
In a case-control study, we performed clinical and molecular genetic examination of 105 AMD patients (48 patients in the early and 57 in the late subgroup) and 95 unrelated healthy controls. Detailed patient histories were recorded with the use of a questionnaire focusing on known risk factors for AMD.


RESULTS
In the early AMD subgroup, homozygous CFH, LOC387715 or HTRA1 polymorphisms conferred a 4.9-fold (95% confidence interval [CI] 1.7-14.2), 7.4-fold (95% CI 2.1-26.2) or 10.1-fold (95% CI 2.5-40.8) risk of disease, respectively. In the late AMD subgroup, carriers of two CFH, LOC387715 or HTRA1 risk alleles were at 10.7-fold (95% CI 3.7-31.0), 11.3-fold (95% CI 3.2-40.4) or 13.5-fold (95% CI 3.3-55.4) greater disease risk, respectively. Two CFH and one LOC387715 risk alleles in combination conferred a 15.0-fold (95% CI 3.2-71.0) increase in risk, whereas two LOC387715 risk alleles combined with one CFH risk allele was associated with a 14.0-fold (95% CI 2.1-95.1) increased risk for late AMD. ApoE alleles neither increased disease risk nor proved to be protective.


CONCLUSIONS
The CFH, LOC387715 and HTRA1 polymorphisms are strongly associated with the development of AMD in the Hungarian population. The association is particularly pronounced when homozygous risk alleles are present and in the late stages of the disease.
Losonczy
Gergely
G
Department of Ophthalmology, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary.
Fekete
Ágnes
Á
Vokó
Zoltán
Z
Takács
Lili
L
Káldi
Ildikó
I
Ajzner
Éva
É
Kasza
Márta
M
Vajas
Attila
A
Berta
András
A
Balogh
István
I
D000368:Aged; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D006814:Hungary; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics*; D011795:Surveys and Questionnaires
C514392:ARMS2 protein, human; D001057:Apolipoproteins E; C493495:CFH protein, human; D011506:Proteins; D017242:Complement Factor H; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases