July 2008
Volume 49, Issue 7
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Retina  |   July 2008
Genotype–Phenotype Correlations for Exudative Age-Related Macular Degeneration Associated with Homozygous HTRA1 and CFH Genotypes
Author Affiliations
  • Nicolas Leveziel
    From the Faculte de Medecine Henri Mondor, Creteil University Eye Clinic, Creteil, France;
    UMRS (Unité Mixte de Recherche en Santé) 538, CHU (Centre Hospitalier Universitaire) Saint Antoine, INSERM (Institut National de la Santé et de la Recherche Médicale), Paris, France;
  • Jennyfer Zerbib
    From the Faculte de Medecine Henri Mondor, Creteil University Eye Clinic, Creteil, France;
  • Florence Richard
    INSERM UMR (Unité Mixte de Recherche) 744, Institut Pasteur de Lille; Université Lille 2, Lille, France;
  • Giuseppe Querques
    From the Faculte de Medecine Henri Mondor, Creteil University Eye Clinic, Creteil, France;
  • Gilles Morineau
    UMRS (Unité Mixte de Recherche en Santé) 538, CHU (Centre Hospitalier Universitaire) Saint Antoine, INSERM (Institut National de la Santé et de la Recherche Médicale), Paris, France;
  • Veronique Fremeaux-Bacchi
    Service d’Immunologie Biologique, Hôpital Européen Georges Pompidou, Paris, France;
    INSERM U255, Paris, France; and
  • Gabriel Coscas
    From the Faculte de Medecine Henri Mondor, Creteil University Eye Clinic, Creteil, France;
  • Gisèle Soubrane
    From the Faculte de Medecine Henri Mondor, Creteil University Eye Clinic, Creteil, France;
  • Pascale Benlian
    UMRS (Unité Mixte de Recherche en Santé) 538, CHU (Centre Hospitalier Universitaire) Saint Antoine, INSERM (Institut National de la Santé et de la Recherche Médicale), Paris, France;
    Faculte de Medecine Pierre et Marie Curie, CHU, Université Pierre et Marie Curie, Saint Antoine, Paris, France.
  • Eric H. Souied
    From the Faculte de Medecine Henri Mondor, Creteil University Eye Clinic, Creteil, France;
Investigative Ophthalmology & Visual Science July 2008, Vol.49, 3090-3094. doi:10.1167/iovs.07-1540
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      Nicolas Leveziel, Jennyfer Zerbib, Florence Richard, Giuseppe Querques, Gilles Morineau, Veronique Fremeaux-Bacchi, Gabriel Coscas, Gisèle Soubrane, Pascale Benlian, Eric H. Souied; Genotype–Phenotype Correlations for Exudative Age-Related Macular Degeneration Associated with Homozygous HTRA1 and CFH Genotypes. Invest. Ophthalmol. Vis. Sci. 2008;49(7):3090-3094. doi: 10.1167/iovs.07-1540.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

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. The purpose was to analyze the angiographic features of patients harboring homozygous genotypes for HTRA1 and CFH genes in a French exudative AMD population.

methods. Two hundred patients affected with exudative AMD were genotyped for the polymorphisms rs11200638 of the HTRA1 gene and rs10611710 of the 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 the 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% RAP. Group 2 (n = 12) presented 50.0% classic and PC, 33.3% occult, no MC CNV 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% classic and PC, 52.9% occult, 11.8% MC, and 5.9% RAP. Occult CNV or MC CNV was 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 in group 3 (50% vs. 10.7%; P < 0.03).

conclusions. This attempt at a genotypic–angiographic correlation in an exudative AMD sample suggests an association between occult or MC CNV and the CFH polymorphism and between classic and PC CNV and the HTRA1 polymorphism.

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the elderly population in Europe and the United States. 1 2 3 4 The exudative AMD is the most rapidly progressive form, with sudden loss of central vision due to leakage or bleeding of choroidal new vessels localized beneath the macular area. Exudative AMD is phenotypically heterogeneous, including different subtypes of choroidal neovascularization (CNV), defined by angiographic criteria, such as classic CNV, predominantly classic (PC) CNV, occult CNV (OCNV), minimally classic (MC) CNV, polypoidal choroidal vasculopathy (PCV), or retinal angiomatosis proliferation (RAP). 5 6 Because AMD is a multifactorial disease including numerous genetic and environmental risk factors, 7 8 9 10 11 12 13 14 15 16 17 18 and with heterogeneous phenotypes, the correlation between any genetic risk factor and phenotype has been difficult to establish to date. 19 20 Furthermore, several genome-wide linkage studies in AMD have been published, and a large number of candidate loci for susceptibility genes have been suggested. 21 22 23 24 25 26 27 28 29 30 Recently, two major loci have been described in association with increased risk of AMD, including the HTRA1/LOC387715 locus at 10q26 and the CFH gene at 1q31. 31 32 33 34 35 36 37 38 39 40 41 42 Our purpose was to analyze the angiographic features of patients with exudative AMD, harboring homozygous status for CFH and HTRA1 polymorphisms. 
Methods
Patients
Two hundred consecutive Caucasian patients harboring exudative AMD in one eye were prospectively recruited at the Creteil University Eye Clinic. Exudative AMD was diagnosed by the investigators (JZ, NL, GQ, EHS, GC, and GS) according to the guidelines from the international classification. 43 Inclusion criteria were age more than 55 years and unilateral exudative AMD. Exclusion criteria were (1) presence of other retinal disease (e.g., diabetic retinopathy, high myopia, or retinal dystrophies), (2) atrophic form of AMD, (3) association of atrophic and exudative forms of AMD, (4) CNV in both eyes at presentation, and (5) fibrovascular scarring that did not allow a precise grading of the phenotype. Each patient underwent complete ophthalmic examination including best corrected visual acuity measurement and fundus examination. Fluorescein angiography (FA; model 50IA camera; Topcon, Tokyo, Japan) was performed for each patient. Furthermore, indocyanine angiography (ICG; HRA, Heidelberg, Germany), and optical coherence tomography (OCT; Carl Zeiss Meditec, Inc., Oberkochen, Germany) were performed when judged necessary by investigators. For classification of the initial lesions, grading of exudative AMD was performed on the earliest FA examination available, before any treatment in any case. Grading was performed before genetic testing separately by each investigator and classified in the following categories: classic or PC CNV, occult CNV, MC CNV, PCV, or RAP. To check the grading, all angiographies were finally submitted to a senior examiner (EHS or GS) for a grading masked from genetic testing. RAP was defined as an anastomosis connecting the chorioretinal circulation to the retinal circulation, commonly associated with a localized intraretinal hemorrhage and hard exudates surrounding the anastomosis. Diagnosis of RAP was made on the basis of FA. When RAP was diagnosed on FA, ICG and OCT where always performed. 44 Diagnosis of vascularized pigment epithelial detachment (PED) was performed on the basis of FA. Both ICG and OCT were performed each time PED was diagnosed on FA to corroborate the diagnosis. Only vascularized PEDs were considered in these exudative AMD eyes. Classification of PEDs as a separate phenotype would result in too small subgroups, and thus drusenoid PED and other types were not considered. 
In addition, a short questionnaire was completed for each patient, including personal and familial history of AMD, tobacco use, and weight and size, to calculate the body mass index (BMI). 
Informed consent was obtained, as required by the French bioethical legislation, in agreement with the Declaration of Helsinki for research involving human subjects, and in agreement with our local ethics committee. 
Genotyping Methods
Genomic DNA was extracted from blood leukocytes by a nonphenolic solvent method with a DNA isolation kit (Puregene; Gentra Systems, Minneapolis, MN). 
Genotyping of the rs11200638 HTRA1 SNP and the Y402H CFH SNP was performed using PCR amplification and direct sequencing. Briefly, we genotyped the SNP (Y402H; rs1061170) located in exon 9 of CFH by PCR-directed sequencing, with the following primer sequences: 5′-GAGTGTTTATTACAGTAAAATTTC-3′ (forward) and 5′-GAAAATCACAGGAGAAATA-3′ (reverse), as previously described. 45 We genotyped the rs11200638 SNP using the following primer sequences: 5′-ATGCCACCCACAACAACTTT-3′ (forward) and 5′-CGCGTCCTTCAAACTAATGG-3′ (reverse). PCR conditions have also been previously described. 41 PCR products were purified using the multiscreen plates according to the manufacturer’s instructions (Millipore, Molsheim, France). Direct DNA sequencing of the purified PCR products was then performed by the dye terminator cycle sequencing method (Applied Biosystems [ABI], Courtaboeuf, France), with a 96-capillary sequencer (model 3700; ABI). Sequence track analysis was performed on computer (Sequencher software; ABI). 
Heterozygous individuals, submitted to a codominant effect, were excluded from the analysis. Homozygous patients were selected, to determine the phenotype of pure genotypes. From the entire cohort, we extracted patients homozygous for CFH and HTRA1 polymorphisms, defining four different groups. 
Group 1 consisted of patients double homozygous for the wild-type (wtwt) allele of the HTRA1 and CFH genes (CFH wtwt/HTRA1 wtwt). Group 2 consisted of patients homozygous for the polymorphism (pp) of the HTRA1 gene, and homozygous for the wild allele of the CFH gene (CFH wtwt/HTRA1 pp). Group 3 consisted of patients homozygous for the polymorphism of the CFH gene, and homozygous for the wild-type allele of the HTRA1 gene (CFH pp/HTRA1 wtwt). Group 4 consisted of patients double homozygous for polymorphisms of both the HTRA1 and CFH genes (CFH pp/HTRA1 pp). 
Statistical Analysis
The four groups were compared for different variables: the categorical variables (all binary) were studied with the Fisher exact test or χ2 test, as appropriate, and the two quantitative variables (age and BMI) were studied with the nonparametric Kruskal-Wallis rank test. Logistic regression models were used to estimate the adjusted odds ratio (OR) with the 95% confidence interval (95% CI). Adjustment variables were age and sex. The Bonferroni correction was applied to multiple comparisons. A difference was said to be significant if it reached P < 0.05. 
Results
Genotypic statuses for both polymorphisms within the entire initial cohort are presented in Table 1 . From the initial cohort of 200 patients with AMD presenting exudative AMD in one eye, 66 patients presented a homozygous status and were included in one of the four groups. It is notable that 8 patients affected with PCV were excluded from the initial cohort. Among the 8 patients with PCV, 2 were observed in group 3, reducing the number of patients from 30 to 28. No PCV was observed in groups 1, 2, or 4. At the diagnosis of CNV, the mean age was 72.8 years (±8.8 SD) in group 1, 71.6 (±7.8) in group 2, 71.1 (±8.0) in group 3, and 69.2 (±7.4) in group 4. Mean age at diagnosis, sex ratio, tobacco use, and BMI did not significantly differ in the four groups (Table 2)
The second grading (senior examiner) was in agreement with the first grading in 54 of 66 cases. In the 12 remaining cases, the final diagnosis was established by EHS and GS together. 
Among the 66 patients with exudative AMD, 35 (53.0%) presented occult CNV only, 18 (27.3%) presented classic and PC CNV, 7 (10.6%) presented MC CNV, and 6 (9.1%) presented RAP. 
Analysis of CNV revealed different angiographic features in the four groups: Group 1 (n = 9) presented three (33.3%) occult CNV, four (44.4%) classic and PC CNV, one (11.1%) MC CNV, and one (11.1%) RAP. Group 2 (n = 12) presented four (33.3%) occult CNV, six (50.0%) classic and PC CNV, no MC CNV, and two (16.7%) RAP. Group 3 (n = 28) presented 19 (67.9%) occult CNV, 3 (10.7%) classic and PC CNV, 4 (14.3%) MC CNV, and 2 (7.1%) RAP. Group 4 (n = 17) presented nine (52.9%) occult CNV, five (29.4%) classic and PC CNV, two (11.8%) MC CNV, and one (5.9%) RAP. 
A comparison between groups 2 and 3 demonstrated that occult CNV or MC CNV was more frequent in group 3 than in group 2 (82.1% vs. 33.3%; P < 0.02) and that classic and PC CNV were more frequent in group 2 than group 3 (50.0% vs. 10.7%; P < 0.03). 
A comparison between the CFH pp (groups 3 and 4) and CFH wtwt (groups 1 and 2) genotypes demonstrated that occult or MC CNV were more frequent in the CFH pp groups (75.6% vs. 38.1%, P < 0.007; Table 3 ). Moreover, classic CNV and PC CNV were more frequent in the CFH wtwt groups than in the CFH pp groups (47.6% vs. 17.8%, P < 0.03). 
A comparison between the HTRA1 pp (groups 2 and 4) and HTRA1 wtwt (groups 1 and 3) genotypes demonstrated that classic and PC CNV were more frequent in the HTRA1 pp groups (37.9 vs. 18;9%), but the difference was not significant (Table 3)
Occult or MC CNV was associated with the homozygous Y402H CFH polymorphism (OR, 6.4 [95% CI: 1.7–23.7], P < 0.02). Classic and PC CNV were more frequently associated with the homozygous HTRA1 polymorphism but not significantly (OR, 2.4 [95% CI: 0.7–8.0]). These results are summarized in Table 4
Discussion
Exudative AMD is a multifactorial disorder characterized by both clinical and genetic heterogeneity. Using on FA, ICGA, and OCT, we attempted to establish a genotype–phenotype correlation between two major at-risk polymorphisms involved in AMD (rs11200638 of HTRA1 and rs10611710 of CFH) and subtypes of exudative AMD. From the initial cohort of 200 patients presenting exudative AMD in one eye only, we selected patients homozygous for wild-type, or for one or both at-risk polymorphisms, with the purpose of selecting four genetically homogenous subgroups. 
Few studies have focused on the phenotypic classification of exudative AMD, including vascularized PED, PCV, and RAP. 46 47 48 49 All these studies confirmed very heterogeneous phenotypes in exudative AMD, and the proportion of each phenotype may vary according to ethnicity. In our entire cohort (n = 200), we observed classic and PC CNV in 22% (n = 44) of cases, MC in 10.5% (n = 21), occult in 52.5% (n = 105), RAP in 11% (n = 22), and PCV in 4% (n = 8). Because polypoidal vasculopathy harbors a distinct clinical presentation and ethnic background, all PCV cases were excluded from the analysis. However, this did not affect the significance of statistical analysis. 
In our series of homozygous patients, we observed 26.5% classic and PC CNV, 10.3% MC CNV, 51.5% occult CNV, 8.8 of RAP, and 2.9% PCV. Our findings are in agreement with those of Cohen et al., 47 who recently observed in the French exudative AMD population classic and PC CNV in 23% of cases, MC in 8.3%, occult in 56.6%, and RAP in 15.1%. 
Despite relatively small series of exudative AMD cases in each subgroup, statistical analysis revealed significant phenotype–genotype correlations. Patients harboring the homozygous Y402H CFH polymorphism only (group 3) were significantly more frequently associated with occult or MC CNV than were patients harboring the homozygous HTRA1 polymorphism only (group 2; respectively, 82.1% vs. 33.3%; P < 0.02). On the other hand, patients harboring the homozygous HTRA1 polymorphism only (group 2) were significantly more frequently associated with classic and PC CNV than were patients harboring the homozygous Y402H CFH polymorphism only (group 3; respectively, 50% vs. 10;7%; P < 0.03). Globally, occult or MC CNV were significantly associated with the polymorphism Y402H of the CFH gene (P < 0.007), and classic and PC CNV were not significantly associated with homozygosity for the at-risk allele of the HTRA1 gene (P = 0.18). However, these results have to be interpreted cautiously; in fact, the power to detect a significant OR of 2.4 after Bonferroni correction was 34% for HTRA1
Recently, investigators in two studies tried to establish genotype–phenotype correlations between the Y402H polymorphism of the CFH gene and exudative AMD in Austria and the United States, respectively. 19 20 Both studies concluded that there was association between at-risk allele C of the Y402H CFH polymorphism, and PC CNV. For homozygous at-risk allele carriers, PC (with occult CNV) lesions were found in 2.4% of exudative AMD cases in the first study 19 and in 47% in the second study. 20 Although a similar conclusion, both studies showed major heterogeneous phenotypic repartition. Furthermore, despite its major role as a susceptibility risk factor for AMD, the status for HTRA1 was not considered in these studies. Environmental factors (nutrition, smoking) that play a major role in AMD should also be considered in larger cohort studies. 
To simplify the phenotypic classification, we selected patients with exudative AMD without atrophy. Because exudative AMD is extremely heterogeneous, and discordant phenotypes can be observed in bilateral cases, we selected individuals affected with exudative AMD in one eye only. 
To simplify the genotypic classification, we decided to analyze only one polymorphism on each locus. For the CFH gene, the Y402H polymorphism appears as one of the most commonly described in association with AMD to date. 32 33 34 35 36 The question of the best polymorphism on locus 10q was raised. However, the HTRA1 and LOC387715 polymorphism are strongly associated by complete linkage disequilibrium, and we decided to analyze the HTRA1 polymorphism. 50  
From these data, perspectives could be to evaluate prospectively the occurrence of CNV in the fellow eye according to the genotype. Furthermore, the analysis of the response to anti-VEGF therapies according to the genotype would be of great interest. These findings could also contribute to enlarging our knowledge of the physiopathologic processes involved in AMD. However, the results in this small series have to be interpreted with caution, considering that discordant phenotypes have been observed in bilateral exudative AMD. Although we present evidence of differences in the distribution of CNV types with different genotypes, it is also clear that a particular genotype is not associated with a single form of CNV. 
In conclusion, this attempt at genotype–phenotype correlation based on angiographic features in a population with exudative AMD suggests an association between occult CNV and the CFH gene. Classic and PC CNV do not appear to be the main phenotype associated with the Y402H CFH polymorphism (P = 0.01). 
 
Table 1.
 
Genotype of the Entire Initial Cohort of Exudative AMD Patients
Table 1.
 
Genotype of the Entire Initial Cohort of Exudative AMD Patients
rs10611710 (CFH)
rs11200638 (HTRAI) TT (wtwt) CT CC (pp)
GG (wtwt) 9 (22.5%) (Group 1) 20 (22.7%) 30 (41.6%) (Group 3)
GA 19 (47.5%) 49 (55.6%) 25 (34.7%)
AA (pp) 12 (30%) (Group 2) 19 (21.5%) 17 (23.6%) (Group 4)
Table 2.
 
Distribution of Exudative AMD Phenotypes in the Four Genetic Subgroups
Table 2.
 
Distribution of Exudative AMD Phenotypes in the Four Genetic Subgroups
Group 1 CFH wtwt HTRA1 wtwt Group 2 CFH wtwt HTRA1 pp Group 3 CFH pp HTRA1 wtwt Group 4 CFH pp HTRA1 pp P
All Groups Groups 2 vs. 3
n 9 12 28 17
Females, n (%) 7 (77.8) 9 (75.0) 17 (60.7) 10 (58.8) NS NS
Age at diagnosis, y, mean (SD) 72.8 (8.8) 71.7 (8.2) 71.6 (7.8) 69.2 (7.4) NS NS
BMI, mean (SD) 26.7 (4.2) 24.9 (2.8) 25.4 (3.8) 28.2 (5.1) NS NS
Tobacco use (%) 1 (14.3) 3 (27.3) 9 (40.9) 6 (35.3) NS NS
C + PC (%) 4 (44.4) 6 (50.0) 3 (10.7) 5 (29.4) 0.057 0.0244
Occult + MC (%) 4 (44.4) 4 (33.3) 23 (82.1) 11 (64.7) 0.0292 0.015
Occult (%) 3 (33.3) 4 (33.3) 19 (67.9) 9 (52.9) NS 0.15
MC (%) 1 (11.1) 0 (0) 4 (14.3) 2 (11.8) NS NS
RAP (%) 1 (11.1) 2 (16.7) 2 (7.1) 1 (5.9) NS NS
Table 3.
 
Phenotypic Features of Exudative AMD in Patients Homozygous for CFH and HTRA1 Polymorphisms
Table 3.
 
Phenotypic Features of Exudative AMD in Patients Homozygous for CFH and HTRA1 Polymorphisms
CFH wtwt CFH pp P HTRA1 wtwt HTRA1 pp P
n 21 45 37 29
Females, n (%) 16 (76.2) 27 (60.0) NS 24 (64.9) 19 (65.5) NS
Age at diagnosis y, mean (SD) 72.1 (8.2) 70.7 (7.7) NS 71.9 (7.9) 70.2 (7.7) NS
BMI, mean (SD) 25.6 (3.4) 26.7 (4.5) NS 25.8 (3.8) 26.9 (4.6) NS
Tobacco use (%) 4 (22.2) 15 (38.5) NS 10 (34.5) 9 (32.1) NS
C + PC (%) 10 (47.6) 8 (17.8) 0.0224 7 (18.9) 11 (37.9) 0.18
Occult + MC (%) 8 (38.1) 34 (75.6) 0.0064 27 (73.0) 15 (51.7) 0.15
Occult (%) 7 (33.3) 28 (62.2) 0.057 22 (59.5) 13 (44.8) NS
MC (%) 1 (4.8) 6 (13.3) NS 5 (13.5) 2 (6.9) NS
RAP (%) 3 (14.3) 3 (6.7) NS 3 (8.1) 3 (10.3) NS
Table 4.
 
OR for Association between Subtypes of CNV and Homozygous Polymorphisms for the CFH or HTRA1 Genes
Table 4.
 
OR for Association between Subtypes of CNV and Homozygous Polymorphisms for the CFH or HTRA1 Genes
HTRA1 OR (95% CI) P CFH OR (95% CI) P
C + PC 2.4 (0.7–8.0) NS 0.2 (0.1–0.8) 0.0406
Occults + MC 0.4 (0.1–1.2) NS 6.4 (1.7–23.7) 0.0112
Occults 0.5 (0.2–1.5) NS 3.4 (1.0–11.8) 0.0994
MC 0.7 (0.1–4.2) NS 4.4 (0.4–43.7) NS
The authors thank Josseline Kaplan for scientific support and Dominique Ducroq for expert technical support. 
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Table 1.
 
Genotype of the Entire Initial Cohort of Exudative AMD Patients
Table 1.
 
Genotype of the Entire Initial Cohort of Exudative AMD Patients
rs10611710 (CFH)
rs11200638 (HTRAI) TT (wtwt) CT CC (pp)
GG (wtwt) 9 (22.5%) (Group 1) 20 (22.7%) 30 (41.6%) (Group 3)
GA 19 (47.5%) 49 (55.6%) 25 (34.7%)
AA (pp) 12 (30%) (Group 2) 19 (21.5%) 17 (23.6%) (Group 4)
Table 2.
 
Distribution of Exudative AMD Phenotypes in the Four Genetic Subgroups
Table 2.
 
Distribution of Exudative AMD Phenotypes in the Four Genetic Subgroups
Group 1 CFH wtwt HTRA1 wtwt Group 2 CFH wtwt HTRA1 pp Group 3 CFH pp HTRA1 wtwt Group 4 CFH pp HTRA1 pp P
All Groups Groups 2 vs. 3
n 9 12 28 17
Females, n (%) 7 (77.8) 9 (75.0) 17 (60.7) 10 (58.8) NS NS
Age at diagnosis, y, mean (SD) 72.8 (8.8) 71.7 (8.2) 71.6 (7.8) 69.2 (7.4) NS NS
BMI, mean (SD) 26.7 (4.2) 24.9 (2.8) 25.4 (3.8) 28.2 (5.1) NS NS
Tobacco use (%) 1 (14.3) 3 (27.3) 9 (40.9) 6 (35.3) NS NS
C + PC (%) 4 (44.4) 6 (50.0) 3 (10.7) 5 (29.4) 0.057 0.0244
Occult + MC (%) 4 (44.4) 4 (33.3) 23 (82.1) 11 (64.7) 0.0292 0.015
Occult (%) 3 (33.3) 4 (33.3) 19 (67.9) 9 (52.9) NS 0.15
MC (%) 1 (11.1) 0 (0) 4 (14.3) 2 (11.8) NS NS
RAP (%) 1 (11.1) 2 (16.7) 2 (7.1) 1 (5.9) NS NS
Table 3.
 
Phenotypic Features of Exudative AMD in Patients Homozygous for CFH and HTRA1 Polymorphisms
Table 3.
 
Phenotypic Features of Exudative AMD in Patients Homozygous for CFH and HTRA1 Polymorphisms
CFH wtwt CFH pp P HTRA1 wtwt HTRA1 pp P
n 21 45 37 29
Females, n (%) 16 (76.2) 27 (60.0) NS 24 (64.9) 19 (65.5) NS
Age at diagnosis y, mean (SD) 72.1 (8.2) 70.7 (7.7) NS 71.9 (7.9) 70.2 (7.7) NS
BMI, mean (SD) 25.6 (3.4) 26.7 (4.5) NS 25.8 (3.8) 26.9 (4.6) NS
Tobacco use (%) 4 (22.2) 15 (38.5) NS 10 (34.5) 9 (32.1) NS
C + PC (%) 10 (47.6) 8 (17.8) 0.0224 7 (18.9) 11 (37.9) 0.18
Occult + MC (%) 8 (38.1) 34 (75.6) 0.0064 27 (73.0) 15 (51.7) 0.15
Occult (%) 7 (33.3) 28 (62.2) 0.057 22 (59.5) 13 (44.8) NS
MC (%) 1 (4.8) 6 (13.3) NS 5 (13.5) 2 (6.9) NS
RAP (%) 3 (14.3) 3 (6.7) NS 3 (8.1) 3 (10.3) NS
Table 4.
 
OR for Association between Subtypes of CNV and Homozygous Polymorphisms for the CFH or HTRA1 Genes
Table 4.
 
OR for Association between Subtypes of CNV and Homozygous Polymorphisms for the CFH or HTRA1 Genes
HTRA1 OR (95% CI) P CFH OR (95% CI) P
C + PC 2.4 (0.7–8.0) NS 0.2 (0.1–0.8) 0.0406
Occults + MC 0.4 (0.1–1.2) NS 6.4 (1.7–23.7) 0.0112
Occults 0.5 (0.2–1.5) NS 3.4 (1.0–11.8) 0.0994
MC 0.7 (0.1–4.2) NS 4.4 (0.4–43.7) NS
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