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J. Hargitai, J. Zernant, J. E. Merriam, Tí. Nagy, R. Allikmets; Analysis of Three Major AMD Loci in the Hungarian Population With Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5104.
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Recent years have seen remarkable advances in determining the genetic cause of age-related macular degeneration (AMD). Variants in three major loci/genes, complement factor H (CFH, on chromosome 1q31), complement factor B (CFB, on 6q) and 3 genes on 10q26, have been associated with increased and/or decreased susceptibility to this complex disorder in the Caucasian population. This study was conducted to determine the extent of involvement of the 3 loci in Hungarian population affected with AMD.
110 individuals diagnosed with AMD and 80 age-matched disease-free control subjects were enrolled in the study. AMD patients were graded into 3 subgroups according to the International classification. Stage 1 included 36 patients with early signs of dry AMD (pigmentary abnormalities); Stage 2 included 39 subjects with early AMD (soft drusen), whereas 35 patients were diagnosed with advanced AMD (CNV or GA). All known (8) informative (i.e., haplotype-tagging) variants from the 3 loci were typed in every study subject and the results were analyzed by standard statistical methods, such as the 2 by 2 table and the Fisher exact test.
The risk allele of the Y402H variant in complement factor H was present in 50% of patients vs. 33.6% of controls (P=0.001; X2=10.2; OR=2.13 [1.3; 3.4]) and the homozygous risk allele of the S69A variant from the 10q locus was present in 17% of AMD patients and in 5% of disease-free individuals (P=0.0005, OR=3.9 [1.7; 9]). One of the two protective haplotypes from the CFB/C2 locus on 6q (tagged by L9H) was also statistically significant (3% in patients vs. 8% in controls; P=0.03), while the other (R32Q) was not. Finally, the homozygous deletion of CFHR1/CFHR3 genes in the CFH locus on 1q31 was strongly protective of the disease by being present in ~9% in the control group and in 2.9% in the AMD group (P=0.02; OR=0.3 [0.09; 0.95]).
In general, genetic analysis of Hungarian AMD population correlated well with similar analyses in other ethnic groups of European origin; i.e., the major risk alleles from CFH/RCA and 10q loci were strongly associated with AMD. The same was true for one of the two protective haplotypes from the CFB/C2 locus. Therefore, the known genetic determinants underlie a major proportion of the disorder also in the Hungarian population; it has to be determined, however, if some of the observed differences from previous studies have an ethnic origin, or if these are due to other factors such as a relatively small sample size.
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