Apolipoprotein E polymorphisms and primary glaucoma in Saudis.

Abstract

The frequencies of apolipoprotein E (APOE) alleles and genotypes were examined in 230 Saudi subjects including primary open-angle glaucoma (POAG; n=60) and primary angle-closure glaucoma (PACG; n=40) patients as well as 130 control subjects.
The presence of glaucoma in patients was based on clinical examination and/or ophthalmic records. The APOE allele frequency (epsilon2, epsilon3, and epsilon4) was studied by polymerase chain reaction (PCR) followed by reverse-hybridization and restriction fragment length polymorphism techniques.
Analysis of data showed a complete absence of epsilon2 allele and a significantly lower frequency of the epsilon3 allele in primary glaucoma patients (90.5%) compared to the control subjects (95.7%, p=0.034, relative risk [RR]=0.473, protective fraction [PF]=0.318). The frequency of the epsilon4 allele was significantly higher in the glaucoma patients (9.5%) compared to the control subjects (4.2%, p=0.034, RR=2.169, etiological fraction [EF]=0.329). The epsilon3/epsilon3 genotype was more common in controls than patients (p=0.060, RR=0.465, PF=0.322). The difference in genotype (epsilon3/epsilon4) was not statistically significant between the two groups (p=0.283). Genotype epsilon4/epsilon4 was found only in 3% of patients while being completely absent in the controls (p=0.080). The genotypes, epsilon2/epsilon2, epsilon2/epsilon3, and epsilon2/epsilon4, were absent in both the test and control groups. When patients were divided on the basis of types of glaucoma, POAG patients had a significantly higher frequency of epsilon4 allele and epsilon4/epsilon4 genotype than controls whereas there was no significant difference between PACG patient and control groups in frequencies of APOE alleles and genotypes.
This study indicates that the epsilon4 allele may be associated with POAG and could be a risk factor while epsilon3 may be protective for POAG, and APOE polymorphisms may not be associated at all with PACG in Saudis.

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Apolipoprotein E polymorphisms and primary glaucoma in Saudis
Najwa Mohammed Al-Dabbagh,1 Nourah Al-Dohayan,1 Misbahul Arfin,2 Mohammad Tariq2
1Department of Ophthalmology, Armed Forces Hospital, Riyadh, Saudi Arabia; 2Research Center, Armed Forces Hospital, Riyadh,
Saudi Arabia
Purpose: The frequencies of apolipoprotein E (APOE) alleles and genotypes were examined in 230 Saudi subjects
including primary open-angle glaucoma (POAG; n=60) and primary angle-closure glaucoma (PACG; n=40) patients as
well as 130 control subjects.
Methods: The presence of glaucoma in patients was based on clinical examination and/or ophthalmic records. The APOE
allele frequency (ε2, ε3, and ε4) was studied by polymerase chain reaction (PCR) followed by reverse-hybridization and
restriction fragment length polymorphism techniques.
Results: Analysis of data showed a complete absence of ε2 allele and a significantly lower frequency of the ε3 allele in
primary glaucoma patients (90.5%) compared to the control subjects (95.7%, p=0.034, relative risk [RR]=0.473, protective
fraction [PF]=0.318). The frequency of the ε4 allele was significantly higher in the glaucoma patients (9.5%) compared
to the control subjects (4.2%, p=0.034, RR=2.169, etiological fraction [EF]=0.329). The ε3/ε3 genotype was more common
in controls than patients (p=0.060, RR=0.465, PF=0.322). The difference in genotype (ε3/ε4) was not statistically
significant between the two groups (p=0.283). Genotype ε4/ε4 was found only in 3% of patients while being completely
absent in the controls (p=0.080). The genotypes, ε2/ε2, ε2/ε3, and ε2/ε4, were absent in both the test and control groups.
When patients were divided on the basis of types of glaucoma, POAG patients had a significantly higher frequency of
ε4 allele and ε4/ε4 genotype than controls whereas there was no significant difference between PACG patient and control
groups in frequencies of APOE alleles and genotypes.
Conclusions: This study indicates that the ε4 allele may be associated with POAG and could be a risk factor while ε3
may be protective for POAG, and APOE polymorphisms may not be associated at all with PACG in Saudis.
Primary glaucoma (PG) is one of the most common eye
diseases that may potentially result in bilateral blindness. It
has been estimated that nearly 66.8 million people worldwide
(around 2%) are affected by glaucoma [1,2]. The disease is
characterized by optic nerve atrophy with an excavated optic
nerve head and progressive visual field loss. The loss of retinal
ganglion cells is the typical pathology in glaucoma [3,4].
Although elevation of intraocular pressure (IOP) is often
related to the optic nerve damage in glaucoma [5], factors
other than IOP are likely to have a role in the pathogenesis of
glaucomatous optic neuropathy, particularly in individuals
with normal tension glaucoma (NTG). Evidence from
population and family studies supports heredity of glaucoma
to be a complex trait. It is a genetically heterogeneous disorder
attributed to the effects of individual causative mutations as
well as interactions of multiple genes with a variety of
environmental factors [6].
Apolipoprotein E (APOE) is the major apolipoprotein in
the central nervous system, which plays an important role in
the uptake and redistribution of cholesterol within neuronal
network [7]. APOE is synthesized by Müller cells (the
Correspondence to: Professor Mohammad Tariq, Ph.D., FRCPath,
FRSC, Sr. Consultant & Director of Research Center, Armed Forces
Hospital, P.O. Box 7897 (W 912), Riyadh, 11159, Saudi Arabia;
Phone: 966 1 4777714 ext. 25602; FAX: 966 1 4777714 ext. 23066;
email: rkhres@yahoo.com
predominant glial cells of the retina), released into the
vitreous, and then transported into the optic nerve through
anterograde rapid transport where it has an important role in
axonal nutrition [8]. It has been suggested that APOE plays a
role in neuronal survival following ischemia and other
chemical insults and that a particular APOE isoform may be
related to neuronal degeneration in glaucoma [9]. The gene
encoding APOE has three polymorphic variants in humans,
these variants are designated as ε2, ε3, and ε4. These variants
differ from one another by the presence of either a C or T
nucleotide at codons 112 and 158. These three alleles encode
different APOE isoforms, which vary significantly in
structure and function including receptor binding capacity and
lipid metabolism [10]. As each individual human being carries
two allelic copies in a gene, six possible genotypes (ε2/ε2, ε3/
ε3, ε2/ε3, ε3/ε4, ε2/ε4, and ε4/ε4) are formed by different
combinations of these three alleles. The frequency of these
genotypes differ significantly among different ethnic groups.
However, APOE ε3/ε3 is the most predominant genotype and
e3 the most common allele in majority of populations [11,
12].
Earlier studies clearly point toward a possible association
between APOE alleles and glaucoma. However, the results of
these studies are contradictory. Some investigators show
positive association [9,13,14] while others show no link at all
[15-17]. More over, earlier studies were mainly restricted to
White populations from Australia [9], United Kingdom [15,
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Received 22 July 2008 | Accepted 28 April 2009 | Published 4 May 2009
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16], and Sweden [17] with only few reports from other ethnic
groups [13,14]. So far, no attempt has been made to study a
possible association between APOE alleles and glaucoma in
a Saudi population.
METHODS
Subjects: The present study was undertaken to evaluate the
association of APOE alleles and genotype with glaucoma in
Saudi primary glaucoma patients. A total of 100 unrelated
Saudi patients with primary glaucoma (primary open-angle
glaucoma [POAG] and primary angle-closure glaucoma
[PACG]) were recruited from the Ophthalmology Clinic of
the Riyadh Military Hospital (Riyadh, Saudi Arabia). The
patient group consisted of 47 males and 53 females with the
age at diagnosis ranging from 30 to 78 years (mean±SD:
58±14.4 years). The control group consisted of 130 unrelated
subjects with 102 males and 28 females and their ages ranging
from 20 to 58 years (mean±SD: 45±11.6 years). The diagnosis
of PG was based on clinical observations.
A comprehensive eye examination was done that
included best-corrected visual acuity (BCVA) measurements
using the logarithm of the minimum angle of resolution
(logMAR) 4-m charts (Light House Low Vision Products,
New York, NY), applanation tonometry, gonioscopy, dilated
fundus examination, optic disc photography, and visual field
(VF) examination. On gonioscopy, an angle was considered
occludable if the pigmented trabecular meshwork was not
visible at an angle greater than 180° in dim illumination. Laser
iridotomy was performed in subjects with occludable angles
after consent was obtained. The ocular biometric
measurements were carried out on the following day.
Visual fields: Automated VFs were performed for all subjects
with a BCVA of 4/16 (logMAR 0.6) or better using frequency-
doubling perimetry (Carl Zeiss Meditec Inc., Dublin, CA). All
eligible subjects underwent C-20-1 screening (if the results
were unreliable or abnormal, the test was repeated) and the
N-30 threshold test. The reliability criteria were no fixation or
false-positive errors for the C-20-1 screening test and less than
20% fixation errors and less than 33% false-positive and false-
negative errors for the threshold N-30 test. Visual fields with
no depressed points to any level of sensitivity were considered
to be normal. A provisional diagnosis of suspected glaucoma
was made when the subject had one or more of the following
conditions: intraocular pressure (IOP) ≥21 mmHg in either
eye, vertical cup-to-disc ratio (VCDR) ≥0.7 in either eye or
cup-to disc ratio (CDR) asymmetry ≥0.2, and focal thinning,
notching, or a splinter hemorrhage. All these subjects were
asked to perform a threshold VF test using the Swedish
interactive threshold algorithm Standard 30-2 program
(model 750, Carl Zeiss Meditec Inc.). A glaucomatous field
defect was diagnosed using a single reliable threshold VF
examination of the central 30° (Swedish interactive threshold
algorithm Standard 30-2). The field was considered to be
abnormal if the Glaucoma Hemifield test results were outside
normal limits and if three or more abnormal contiguous non-
edge points (except the nasal horizontal meridian) were
depressed to p<0.05 [18]. Reliability criteria were as
recommended by the instrument’s algorithm (fixation losses
<20%; false-positive and false-negative <33%).
Diagnostic definitions: The distribution of VCDR and IOP
was obtained from those subjects with reliable and normal
supra-threshold VF testing using frequency-doubling
perimetry. Cases of glaucoma were defined using the
International Society of Geographical and Epidemiologic
Ophthalmology classification [19]. Glaucoma was classified
according to three levels of evidence. In category 1, diagnosis
was based on structural and functional evidence. Using the
Swedish interactive threshold algorithm 30-2, it required CDR
or CDR asymmetry greater than 97.5th percentile for the
normal population, or a neuroretinal rim width reduced to 0.1
CDR (between 10- and 1-o’clock or 5- and 7-o’clock) with a
definite VF defect consistent with glaucoma. Category 2 was
based on advanced structural damage with unproven field
loss. This included those subjects in whom VFs could not be
determined or were unreliable, and subjects with CDR or
CDR asymmetry greater than 99.5th percentile for the normal
population. Lastly, category 3 consisted of persons whose
optic discs could not be examined because of media opacities
and with an IOP greater than 99.5th percentile for the normal
population.
Blindness was defined as a best-corrected logMAR visual
acuity of less than 2/40 (log MAR 1.3) and/or constriction of
the VF to less than 10° from fixation in the better eye [20].
Hyperopia was defined as spherical equivalent greater than
0.50 diopters in a phakic eye [21]. Diabetes mellitus was
detected based on the current use of antidiabetic medication
and/or a random blood glucose level greater than 200 mg/dl
[22].
Thus, the primary glaucoma patients were separated into
two groups (POAG and PACG) using the following criteria.
POAG: The patients with open anterior chamber angles on
gonioscopy, typical glaucomatous cupping of optic disc and
visual field defects characteristic of glaucoma were classified
as POAG. PACG: The patients with partially or totally closed
anterior chamber angle (appositional angle closure or
synechiae in angle) along with damaged glaucomatous optic
disc or defective glaucomatous visual field were classified as
PACG. Subjects with any sign of secondary angle closure
(e.g., uveitis, lens related glaucoma; microspherophakia;
evidence of neovascularization in the angle and associated
retinal ischemia or congenital angle anomalies) were
excluded. Patients with signs of intracranial disease that
would cause optic nerve atrophy in X-ray computerized
tomography or magnetic resonance imaging were also
excluded.
Venous blood was collected and stored at −20 °C before
the extraction of DNA. The study protocol was approved by
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the ethics committee of Riyadh Military Hospital, and
informed consent was obtained from all study participants.
Genotyping: The genotypes of the APOE polymorphisms
were determined using the ApoE StripAssayTM kit (ViennaLab
Labordiagnostika GmbH, Vienna, Austria), which is based on
polymerase chain reaction (PCR) and reverse-hybridization
techniques. The procedure included three steps: (1) DNA
isolation, (2) PCR amplification using biotinylated primers,
and (3) hybridization of amplification product to a test strip
containing allele-specific
immobilized as an array of parallel lines. Bound biotinylated
sequences were detected using streptavidin-alkaline
phosphatase and color substrates. To cross-check the results,
the genotypes of the APOE polymorphisms were also
determined by PCR and restriction fragment length
polymorphism (RFLP) technique. Primers were designed on
the basis of the sequence data for APOE available in GenBank
to amplify the coding sequence of APOE. PCR was performed
using PuRe Taq Ready-To-Go
(Amersham Biosciences, Piscataway, NJ) with the following
primers: forward primer: 5- GAC GCG GGC ACG GCT GTC
CAA GGA GCT GCA GGC GAC GCA GGC CCG GCT
GGA CGC GGA CAT GGA GGA-3 and reverse primer: 5 -
AGG CCA CGC TCG ACG CCC TCG CGG GCC CCG GCC
TGG TAC ACT-3.
Genomic DNA was extracted from whole blood using a
commercial kit (QIAmp; Qiagen, Hilden, Germany).
Genomic DNA (200-300 ng) was used as a template in 25 μl
reactions. Genomic DNA was amplified for 40 cycles. Each
cycle consisted of 94 °C for 30 s, 68 °C for 10 s, and 72 °C
for 1 min. PCR products obtained were separated by
electrophoresis on 1.5% agarose gel in Tris-acetic acid-EDTA
(TAE) buffer and visualized by ethidium bromide
fluorescence. Fragments with the expected size were cut from
the gel and purified using GFX PCR DNA Gel band
purification kit (Amersham). Purified DNA was digested with
the CfoI (HhaI) enzyme and separated by agarose gel
electrophoresis to identify the genotype. On the basis of size
and number of various fragments generated, APOE genotypes
were determined as ε2/ε2 with 144 bp and 96 bp fragments;
ε3/ε3 with 144 bp and 48 bp fragments; ε4/ ε4 with 72 bp and
48 bp fragments; ε2/ε3 with 144 bp, 96 bp, and 48 bp
fragments; ε3/ ε4 with 144 bp, 72 bp, and 48 bp fragments; and
ε2/ε4 with 144 bp, 96 bp, 72 bp, and 48 bp fragments. The
prevalence of various genotypes in patients and controls was
determined. Complete matching of results was obtained
following both of the above mentioned procedures.
Statistical analysis: Frequencies of various alleles and
genotypes for each polymorphism were compared between
patients and controls and then analyzed by Fisher’s exact test
(p values less than 0.05 were considered significant). The
strength of the association of disease with respect to a
particular antigen is expressed by an odds ratio interpreted as
oligonucleotide probes
PCR Beads
relative risk (RR) according to Woolf's method as outlined by
Schallreuter et al. [23]. The RR was calculated only for those
alleles and genotype that were increased or decreased in
glaucoma patients as compared to normal Saudis.
Etiologic fraction: The etiologic fraction (EF) indicates the
hypothetical genetic component of the disease. Values greater
than 0.0 were considered significant. It was calculated for
positive association (RR>1) [24].
Preventive fraction: The preventive fraction (PF) indicates the
hypothetical protective effect of one specific antigen for the
disease. It was calculated for negative association (RR<1)
[24]. Values less than 1.0 indicated the protective effect of the
genotype/allele against the manifestation of the disease.
RESULTS
Out of 100 PG patients, 60 were diagnosed as having POAG
and 40 as having PACG. Diagnosis of POAG was based on
category 1 in nine subjects (15%) and category 2 in 51 subjects
(85%). Between category 1 and category 2, there were no
significant differences in age, IOP, or gender distribution. One
subject was blind in both eyes, and one subject had unilateral
blindness due to POAG. There were 40 subjects with PACG.
Diagnosis was based on category 1 in 10 subjects (25%),
category 2 in 28 subjects (70%), and category 3 in two subjects
(5%). Two subjects (5%) were bilaterally blind and three
(7.5%) were unilaterally blind, all due to PACG.
The frequency results of APOE alleles and genotypes in
the PG patients and the control subjects are summarized in
Table 1 through Table 6. The frequency of the ε3 allele was
significantly lower in the glaucoma patients (90%) than in the
control subjects (95.7%, p=0.034, RR=0.473, PF=0.318). In
contrast, the frequencies of the ε4 allele was significantly
higher in the glaucoma patients than in the controls (9.5%
versus 4.2%, p=0.034, RR=2.169, EF=0.329). The allele ε2
was absent in both the patient and control groups (Table 1).
Our study on various genotypes of APOE also showed
variations in patient and control groups (Table 2). The
prevalence of ε3/ε3, ε3/ε4, and ε4/ε4 was 84%, 13%, and 3%
in patients and 91.5%, 8.4%, and 0% in the control group,
respectively. Though the ε3/ε3 genotype was more common
in both the test and control Saudi population, the statistical
analysis of data showed a nearly significant difference in ε3/
ε3 genotype frequencies between patients and controls
(p=0.060, RR=0.465, PF=0.322). The difference in the
frequencies of the second common genotype (ε3/ε4) was not
statistically significant between the two groups (p=0.283).
Genotype ε4/ε4 was found only in 3% of patients while being
completely absent in the controls (p=0.080). The genotypes
ε2/ε2, ε2/ε3, and ε2/ε4 were absent in both the groups. These
results indicated that the ε4 allele is associated with glaucoma
and can be a risk factor while the ε3 allele may be protective
in Saudis. The frequencies of various genotypes and alleles
were almost similar in male and female patients, clearly
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indicating that gender plays no role in genotype/allele
distributions among populations (Table 3).
Though the distribution of APOE genotypes and alleles
was not significantly different in the two types of glaucoma
(Table 4), significant difference was found in the frequencies
of the ε4/ε4 genotype and the ε4 and ε3 alleles between the
POAG patients and controls when each glaucoma group was
compared with the controls separately. The frequencies of the
ε4/ε4 genotype and the ε4 allele were significantly higher in
POAG patients than in controls (p=0.03 and p=0.02,
respectively; Table 5). The frequency of the ε3 allele was
significantly higher in controls (p=0.02). Moreover, the
frequencies of various APOE genotypes and alleles differed
between PACG and controls, but the differences were not
statistically significant (Table 6), indicating that the ε4/ε4
genotype and ε4 allele are only significantly associated with
POAG and not with PACG in Saudis.
DISCUSSION
The results of this study showed the complete absence of the
APOE ε2 allele but a very high frequency (95.7%) of ε3. The
TABLE 1. DISTRIBUTION OF APOE ALLELE FREQUENCIES IN GLAUCOMA PATIENTS AND MATCHED CONTROLS.
Glaucoma (n=200)
Control (n=260)
Number
11
249
0
p value RR
0.034
0.034
-
EF*/PF
0.329*
0.318
-
Number
19
181
0
Frequency (%)
9.5
90.5
0
Frequency (%)
4.2
95.7
0
ε4
ε3
ε2
2.169
0.473
-
Number of subjects=n. Values with asterisk (last column) correspond to etiological fraction (EF) while values without asterisk
indicate protective fraction (PF).
TABLE 2. DISTRIBUTION OF APOE GENOTYPE FREQUENCIES IN GLAUCOMA PATIENTS AND MATCHED CONTROLS.
Genotype
ε3/ε3
ε3/ε4
ε4/ε4
ε2/ε2
ε2/ε3
ε2/ε4
Glaucoma (n=100)
Control (n=130)
p value RR
0.06
0.283
0.08
-
-
-
EF*/PF
Number
84
13
3
0
0
0
Frequency (%)
84
13
3
0
0
0
Number
119
11
0
0
0
0
Frequency (%)
91.5
8.4
0
0
0
0
0.465
1.616
-
-
-
-
0.322
0.2063*
-
-
-
-
Number of subjects=n. Values with asterisk (last column) correspond to etiological fraction (EF) while values without asterisk
indicate protective fraction (PF).
TABLE 3. COMPARISON OF APOE GENOTYPES AND ALLELES FREQUENCIES IN MALE AND FEMALE GLAUCOMA PATIENTS.
Genotype/Allele
ε3/ε3
ε3/ε4
ε4/ε4
ε3
ε4
p value
0.999
0.377
0.243
0.636
0.636
Number
40
8
0
88
8
Frequency (%)
83.33
16.66
0
91.66
8.33
Number
44
5
3
93
11
Frequency (%)
84.61
9.61
5.76
89.42
10.57
Number of subjects=n.
TABLE 4. COMPARISON OF APOE GENOTYPE AND ALLELE FREQUENCIES IN PATIENTS WITH POAG AND PACG.
Genotype/Allele
ε3/ε4
ε4/ε4
ε3/ε3
ε4
ε3
Open angle glaucoma
(n=60)
7 (11.66)
3 (5.00)
50 (83.33)
13 (10.83)
107 (89.16)
Angle closure glaucoma
(n=40)
6 (15)
0
34 (85)
6 (7.5)
74 (92.5)
p value
0.76
0.27
0.99
0.47
0.47
Number of subjects=n; values are indicated as n (%).
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915
Allele
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frequency of ε4 (known as the thrifty allele) was 4.3% in this
Saudi population. Global studies on the APOE locus have
shown highly significant variations in the allele frequencies of
ε2 (0%–12%), ε3 (75%–90%), and ε4 (6%–20%) [25-31]. The
reason for the dissimilar findings in different populations is
far from clear and may reflect a regional difference in the
APOE genotype frequencies. The ε3 allele is the most frequent
in all the human groups, especially in populations with a long
established agricultural economy whereas the APOE ε4 allele
remains higher in populations where the economy of foraging
still exists or where the food supply is/was scarce and
sporadically available [32].
Results of the present study revealed significant
differences in the frequencies of ε3 and ε4 alleles between the
glaucoma patient and the control group (Table 1). The ε3 allele
was more common in controls while the ε4 allele was
predominant in glaucoma patients, suggesting that the
inheritance of the ε4 allele might be a risk factor whereas ε3
may exert a protective effect for glaucoma in the Saudi
population. Our findings are in agreement with Yilmaz et al.
[33] who reported a protective role of APOE ε3 allele in
patients with exfoliation syndrome (a disease closely
associated with glaucoma) in the Turkish population. The
neuroprotective effect of ε3 is evident from several earlier
studies [34,35]. APOE has an isoform-specific effect on
neuronal growth with ε3 stimulating neuronal elongation and
neurite outgrowth on the dorsal root ganglion [34]. In
individuals with acute cerebral ischemia such as an
intracerebral hemorrhage, the ε3 allele confers a much higher
rate of survival and functional recovery whereas ε4 leads to a
higher rate of disability and mortality [35].
Moreover, the results of this study clearly suggest that the
presence of ε4 has a negative impact as its presence was found
to be associated with high risk of POAG. Vickers et al. [9]
also reported an association between the ε4 allele and NTG in
the Tasmanian population. Recently, Yaun et al. [36] reported
that the ε4 allele may be a latent risk factor in developing
primary glaucoma in the Chinese population. On the other
hand, Liew et al. [37] found a weak association between
APOE ε4 and retinal microvascular degeneration.
Contrary to these findings, a decreased risk of NTG in
Chinese [13,14] and POAG in Japanese [38] has been reported
whereas some investigators reported no link between APOE
polymorphisms and glaucoma. Besides glaucoma, the APOE
ε4 allele has been identified as a genetic susceptibility factor
for a variety of neurodegenerative disorders in diverse ethnic
populations [39-42]. The APOE ε4 allele has also been
associated with early age-at-onset of Alzheimer’s Disease
(AD) in a dose-dependent manner [43,44]. Interestingly, a
high incidence of glaucoma in AD patients clearly suggests a
close association between these neurodegenerative disorders
[45,46]. It has been hypothesized that the cellular mechanisms
involved in the degeneration of optic nerve cells in glaucoma
are quite similar to the neurodegenerative changes in AD [9,
47,48]. The APOE ε4 allele is also strongly linked with
increased risk of Parkinson disease, schizophrenia, and
coronary artery disease [49-55]. Possession of the ε4 allele is
also associated with a retarded recovery after traumatic head
injury [56,57].
APOE alleles modulate the biological functions of APOE
in part by altering the binding of the different lipoprotein lipid
classes [49]. Individuals carrying the ε4 allele have higher
plasma and neuronal levels of cholesterol as compared to
TABLE 5. DISTRIBUTION OF APOE GENOTYPE AND ALLELE FREQUENCIES IN PATIENTS WITH POAG AND MATCHED CONTROLS.
Genotype/Allele
ε3/ε4
ε4/ε4
ε3/ε3
ε4
ε3
Open angle glaucoma (n=60)
7 (11.66)
3 (5.00)
50 (83.33)
13 (10.83)
107 (89.16)
Controls (n=130)
11 (8.4)
00
119 (91.5)
11 (4.2)
249 (95.7)
p value
0.59
0.03
0.13
0.02
0.02
RR
1.428
-
0.462
2.75
0.363
EF*/PF
0.113*
-
0.255
0.034*
0.034
Number of subjects=n; values are indicated as n (%). Values with asterisk (last column) correspond to etiological fraction (EF)
while values without asterisk indicate protective fraction (PF).
TABLE 6. DISTRIBUTION OF APOE GENOTYPE AND ALLELE FREQUENCIES IN PATIENTS WITH PACG AND MATCHED CONTROLS.
Genotype/Allele
ε3/ε4
ε4/ε4
ε3/ε3
ε4
ε3
Angle closure glaucoma (n=40)
6 (15)
0
34 (85)
6 (7.5)
74 (92.5)
Controls (n=130)
11 (8.4)
00
119 (91.5)
11 (4.2)
249 (95.7)
p value
0.236
-
0.236
0.246
0.246
RR
1.909
-
0.523
1.835
0.544
EF*/PF
0.167*
-
0.168
0.160*
0.161
Number of subjects=n; values are indicated as n (%). Values with asterisk (last column) correspond to etiological fraction (EF)
while values without asterisk indicate protective fraction (PF).
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individuals with the ε2 or ε3 allele. The higher frequency of
the ε3/ε3 genotype in controls when compared to the
glaucoma patients indicated a protective effect of ε3/ε3
against the development of glaucoma in Saudis. On the other
hand, the ε4/ε4 genotype was only found in the patient group
with a complete absence in the normal Saudi population,
suggesting its association with POAG. The genotypes ε2/ε2,
ε2/ε3, and ε2/ε4 were absent in both the patient and control
groups. Earlier studies on APOE polymorphisms in the
general population also showed the absence of genotypes
containing the ε2 allele among Saudis [58] as well as Native
Americans [59].
The results of this study suggest that APOE alleles may
influence the risk of POAG but has no effect on the
susceptibility of PACG. The inheritance of the ε4 allele is
associated with elevated risk of POAG but not of PACG, and
ε3 may exert protection against POAG. However, further
studies involving larger number of patients are warranted to
reach a definite conclusion.
ACKNOWLEDGMENTS
The authors would like to thank S. Sadaf Rizvi for her help in
laboratory work.
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