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Association of ABO blood groups with glaucoma

in the Pakistani population

Muhammad Imran Khan,* MS; Shazia Micheal,* MS; Farah Akhtar, MBBS, DOMS, FCPS (Ophth);
Akhtar Naveed, MBBS, DO, MCPS (Ophth); Asifa Ahmed,* PhD; Raheel Qamar,* PhD
Objective: To study the association of blood groups with different types of glaucoma including primary open-angle
glaucoma (POAG), primary closed-angle glaucoma (PCAG), and pseudoexfoliative glaucoma (PEXG) in the Pakistani population.
Study Design: The present study was a prospective case control study.
Participants: ABO and Rh blood groups were analyzed in 2046 controls and 477 glaucoma patients (220 POAG,
146 PCAG, and 111 PEXG).
Methods: Hemagglutination patterns were used to determine the prevalence of the ABO and Rh blood groups in all
the subjects. Logistic regression analysis was carried out to evaluate any association of the different blood groups
with glaucoma.
Results: In the present study, the percentage of blood groups A, B, AB, and O in patients was found to be 19%, 41%,
10%, and 30%, and in the control group, the values were 26%, 31%, 12%, and 31%, respectively. A signicant positive
association was found between the B blood group and glaucoma (p value < 0.05, odds ratio [OR] 1.5, and F2 15.8).
Logistic regression analysis revealed that the blood group B was associated with all types of glaucoma with OR
of 1.35 (95% CI 1.011.80; p = 0.04) for POAG, 1.71 (95% CI 1.212.40; p = 0.002) for PCAG, and 1.61 (95% CI
1.092.36; p = 0.016) for PEXG. POAG was also found to be associated with the Rh allele (p < 0.05) with an OR
of 4.05 (95% CI 2.985.51), as compared with controls.
Conclusions: In the Pakistani patient cohort, blood group B is associated with all types of glaucoma and the Rh
allele is associated only with POAG.
Objet : tude de lassociation des groupes sanguins aux divers types de glaucome, y compris le glaucome primaire
angle ouvert (GPAO), le glaucome primaire angle ferm (GPAF) et le glaucome pseudoexfoliatif (GPEX) chez la
population pakistanaise.
Nature : tude prospective avec cas tmoins.
Participants : Analyse des groupes sanguins ABO et Rh chez 2046 tmoins et 477 patients glaucomateux (220
GPAO, 146 GPAF et 111 GPEX).
Mthodes : Des modes dhmagglutination ont servi tablir la prvalence des groupes sanguins ABO et Rh chez
tous les sujets. Lanalyse de rgression logistique a permis dvaluer toute association des divers groupes sanguins
au glaucome.
Rsultats : Dans la prsente tude, le pourcentage des groupes sanguins A, B, AB et O parmi les patients a t valu
19 %, 41 %, 10 % et 30 %, et chez le groupe tmoin les valeurs furent 26 %, 31 %, 12 %, et 31 %, respectivement.
Une association signicativement positive a t constate entre le groupe sanguin B et le glaucome (valeur p <
0,05, rapport de cote [RC] 1,5, et F2 15,8). Lanalyse de rgression logistique a rvl que le groupe sanguin B tait
associ tous les types de glaucome avec un RC de 1,35 (95 % CI 1,011,80; p = 0,04) pour le GPAO, 1,71 (95 % CI
1,212,40; p = 0,002) pour le GPAF, et 1,61 (95 % CI 1,092,36; p = 0,016) pour le GPEX. On a aussi constat que
le GPAO tait associ lallle RH (p < 0,05) avec un RC 4,05 (95 % CI 2,985,51), comparativement aux tmoins.
Conclusions : Chez la cohorte de patients pakistanais, le groupe sanguin B est associ tous les types de glaucome
et lallle RH est associ seulement au GPAO.

laucoma affects more than 70 million people worldwide and has been shown to be the second-leading
cause of blindness after cataract. Glaucoma is classied
into primary and secondary glaucoma; there are various
types of primary glaucoma in which the eye does not have
any preexisting disease, the most common being primary

open-angle glaucoma (POAG) and primary closed-angle

glaucoma (PCAG). As opposed to this, patients with glaucoma who had any preexisting eye disease are diagnosed
with secondary glaucoma, which includes pseudoexfoliative
glaucoma (PEXG).15 Signicant associations have been
observed previously between the blood groups and differ-

From *the Department of Biosciences, COMSATS Institute of

Information Technology, Islamabad, Pakistan; Al-Shifa Trust Eye Hospital,
Rawalpindi, Pakistan; Christian Hospital, Taxila, Pakistan; and Shifa
College of Medicine, Islamabad, Pakistan

Correspondence to Raheel Qamar, PhD, COMSATS Institute of

Information Technology, Park Rd., Chak Shahzad, Islamabad-44000,

Originally received Oct. 22, 2008. Revised Mar. 11, 2009

Accepted for publication Mar. 25, 2009
Published online Sep. 1, 2009



This article has been peer-reviewed. Cet article a t valu par les pairs.
Can J Ophthalmol 2009;44:5826

ABO blood groups and glaucomaKhan et al.

ent diseases, which include, among others, coronary heart
disease,6 ulcus ventriculi,7 gastritis,8 and leukemia.9,10 Eye
diseases such as myopia, nuclear cataract, and convergent
squint have also been shown to have an association with
the blood group O.11 In contrast, some researchers have reported no signicant association of myopia and cataracts
with ABO blood groups.12,13 Several reports have appeared
in recent years that have suggested a link between glaucoma
and blood groups. In studies carried out in populations of
India,14 Tunisia,15 and Iran,16 an association has been observed between glaucoma and blood groups. A possible explanation for this is that the glaucoma susceptibility loci
have been mapped to chromosomes 1 and 9, which also
contain the loci for the ABO blood group antigen and the
Rh factor.17 We were interested in studying the association
of blood groups with different types of glaucoma in the
Pakistani population. The present study was thus designed
and conducted on a substantially larger number of affected
and normal controls, as compared with earlier reported
studies, to obtain a higher degree of statistical reliability.

The present prospective case control cross-sectional study

was carried out on 477 glaucomatous patients visiting the
glaucoma clinic of Al-Shifa Trust Eye Hospital, Rawalpindi,
and the Christian Hospital, Taxila. Of the 477 glaucoma
patients who were analyzed, 220 cases were of POAG,
146 were of PCAG, and 111 were of PEXG. The 2046 controls were taken from the general population who had no
previously reported eye disease.
Complete ophthalmic examination of all the patients was
carried out before the selection of the patients, which included slit-lamp biomicroscopy, visual acuity with the help
of Snellen chart, intraocular pressure measured with Goldman applanation tonometer, visual eld defects determined
with Humphrey 30-2, indirect fundoscopy to determine
cup-to-disc ratio, B scan to identify typical glaucomatous
cupping of the optic disc, and gonioscopy to assess the type
of glaucoma.
This study conforms to the Declaration of Helsinki and
was approved by the Departmental Ethics Committee. All
subjects, including patients and controls, were informed
verbally about the study in their local language. In addition, a written informed consent was obtained from them,
after which a 2 mL venous blood sample was taken. The
determination of the ABO and Rh blood group was then
carried out. Briey, 4 drops of blood were placed on 4 different glass lamellas and then on each, a drop of either antiA, anti-B, anti-AB, or anti-D was added and agglutination
was observed within 1 to 3 minutes. The blood groups of
the samples were then classied, based on their agglutination patterns.
The data were then collated and statistical analyses were
performed using SPSS statistical software for Windows, v.
12.0 (SPSS Inc, Chicago, Ill.). Odds ratio (OR) and 95%

condence interval (95% CI) were calculated by logistic regression. POAG, PCAG, and PEXG patients and controls
were compared with the F2 test.

In the present study, 477 glaucoma patients and 2046

normal controls were analyzed to study the association
of the ABO blood group with glaucoma in the Pakistani
population. Patients were categorized into 3 types: PCAG,
consisting of 146 patients with a mean age of 55.3 (SD 9.5)
years (65.3% male and 34.7% female); POAG, consisting
of 220 patients with a mean age of 61.7 (SD 15.5) years
(63.2% male and 36.8% female); and PEXG, consisting
of 111 patients with a mean age of 65.5 (SD 16.5) years
(77.7% male and 22.3% female). Of the 2046 controls,
64.2% were male and 35.8% were female and their overall
mean age was 58.2 (SD 8.6) years.
The adequacy of the sample size was determined with the
help of power analysis (G POWER, v. 2.0, www.psycho. For POAG,
PCAG, and PEXG, this gave a value of 1.00, 1.00, and
0.99, respectively, at 0.05 value of alpha, which indicates
that the sample sizes in the 3 groups were adequate for the
The percentage of blood group A, B, AB, and O in the
total glaucoma patients (data of all the groups combined
together) was 19%, 41%, 10%, and 30%, whereas in the
controls, these values were 26%, 31%, 12%, and 31%, respectively. When the blood groups of the glaucoma patients
were compared with the controls, blood group B was found
to be signicantly associated with glaucoma, with a p value
< 0.05 and OR of 1.51 (95% CI 1.231.86) (Table 1).
Similarly, the association of blood groups was studied in
the patients and controls in the different types of glaucoma.
This revealed that blood group B was strongly associated
with all types of glaucoma, with a p value of 0.040 for
POAG, 0.002 for PCAG, and 0.016 for PEXG, and ORs
Table 1Comparison of glaucoma patient blood group and
n (%)

n (%)


p value

1802 (88)

359 (75) 0.41 (0.320.53)



244 (12)

118 (25) 2.42 (1.893.11)




538 (26)
478 (23)

90 (19) 0.65 (0.510.84)

65 (14) 0.52 (0.390.68)




642 (31)
575 (28)


242 (12)
199 (10)


624 (31)
550 (27)

Blood group
ABO (Total)

A (Total)
B (Total)
AB (Total)
O (Total)

60 (3)

67 (3)

43 (2)


74 (4)

25 (5)

OR (95% CI)

1.82 (1.142.94)



195 (41) 1.51 (1.231.86)

161 (34) 1.3 (1.051.61)



2.27 (1.493.46)



50 (10) 0.87 (0.631.20)

35 (7) 0.73 (0.511.07)



34 (7)

1.51 (0.842.72)



142 (30) 0.97 (0.781.20)

98 (21) 0.7 (0.550.90)

15 (3)





44 (9)

2.71 (1.843.98)

Note: OR, odds ratio.



ABO blood groups and glaucomaKhan et al.

of 1.35 (95% CI 1.011.80), 1.71 (95% CI 1.212.40),
and 1.61 (95% CI 1.092.36), respectively (Table 2).
The prevalence of Rh factor was also studied in controls
and glaucoma patients; in the controls, 88% of the samples
were Rh positive (Rh) and 12% of the samples were R
negative (Rh), whereas in the glaucoma patients, these
values were 75% and 25%, respectively. Statistical analysis
of this distribution reveals that the Rh allele is associated
with glaucoma, p value < 0.05, and OR of 2.42 (95% CI
1.893.11) (Table 1). When studying the association of
the different types of glaucoma separately with the Rh factor, only POAG was found to be associated with the Rh
allele, p value < 0.05, and OR of 4.05 (95% CI 2.985.51),
whereas the other types of glaucoma did not have any statistically signicant association with the Rh factor (Table 2).
All the data were also analyzed to see if there were any
gender differences among the glaucoma groups as well as
the controls, but no such difference was observed in the
various parameters.

The current study reveals that blood group B was more

signicantly associated with glaucoma when the patients
were compared with the control subjects. There was no association between other types of ABO blood groups and the
different types of glaucoma. Also, the Rh allele was found
to be signicantly more prevalent in the patients suffering
from POAG, as compared with the controls and those with
other types of glaucoma (PCAG and PEXG).
In the literature, there are conicting ndings of an association between the ABO blood groups and the different
types of glaucoma in different ethnic groups. In one study,
Leske et al.18 did not nd any association between POAG
and the ABO blood groups. Garg and Pahwa14 reported
that the frequencies of blood groups A and B were higher
in POAG and PCAG, whereas the frequencies of the blood
groups AB and O were signicantly lower. Similar ndings

were documented in a study conducted in Iran, in which

blood group B was found to be more prevalent in primary
congenital glaucoma when compared with controls.16 We
have also observed a signicant association of blood group
B with the different types of glaucoma when compared with
controls, the association being highest in PCAG. In contrast
to our results, a study conducted in Tunisia reported that the
AB blood group seems to be a genetic marker of POAG.15
However, our data do not indicate any association of blood
group AB with any of the different types of glaucoma in the
Pakistani population, which is consistent with the ndings
reported in the Iranian population.16 This is not surprising
because Pakistan shares a genetic history with Iran; while
studying the Y chromosomal markers, Quintana-Murci et
al.19 showed that there is a signicant similarity in the genetic makeup of different Pakistani ethnic groups to Iranian
ethnic groups, on the basis of which they proposed a migration route of populations from Iran to Pakistan, resulting in
the peopling of the latter. It is worth pointing out that the
conicting reports in the literature concerning the association of the ABO blood group with glaucoma are probably
due to genetic variations in the different populations that
were studied. It has been shown that the distribution of the
blood groups varies among different countries and ethnic
groups, and even in populations that reside in proximity;
thus, any data obtained based on blood groups as markers
should be used very carefully for diagnostic purposes because cross-comparisons between populations will not yield
relevant results.
The inheritance pattern of glaucoma is very complex; it
has been shown to be inherited in an autosomal dominant
or recessive trait, or as a complex trait with multifactorial
genes being involved. Different genetic studies have localized the chromosomal locations of genes involved in the
complex forms of the disease.17 Recently, it has been seen
in the Pakistani population that a single nucleotide change
C677T in the methylenetetrahydrofolate reductase gene
present on chromosome 1 is associated with PCAG.20 The

Table 2Comparison of the blood group of different types of glaucoma (POAG, PCAG, and PEXG) with controls

n (%)

ABO (Total)

n (%)


p value

n (%)

OR (95% CI)


p value

n (%)

OR (95% CI)


p value

0.24 (0.180.34) 90.2


126 (86) 0.85 (0.511.43)



91 (82) 0.61 (0.371.01)



244 (12)

78 (35)

4.05 (2.985.51) 90.2


20 (14) 1.17 (0.691.96)



20 (18) 1.62 (0.9512.74) 3.09



538 (26)
478 (23)

44 (20)
28 (13)

0.70 (0.490.98) 4.12 0.04

0.48 (0.320.72) 12.95 <0.001

22 (15) 0.5 (0.310.79)

19 (13) 0.49 (0.300.80)



24 (21) 0.77 (0.491.22)

18 (16) 0.63 (0.381.05)



60 (3)

16 (7)

2.60 (1.484.56) 11.54





642 (31)
575 (28)

84 (38)
64 (29)

1.35 (1.011.80)
1.05 (0.771.42)




67 (3)

20 (9)

2.95 (1.764.95) 18.2

1.1 (0.412.97)




242 (12)
199 (10)

24 (11)
14 (6.5)

0.91 (0.591.42)
0.63 (0.361.09)


14 (13) 1.08 (0.611.90)

10 (9) 0.92 (0.481.77)



43 (2)

10 (4.5)

2.22 (1.114.42)




624 (31)
550 (27)

68 (31)
36 (16)

1.02 (0.751.38) 0.02

0.53 (0.370.77) 11.46

74 (4)

32 (15)

4.54 (2.937.03) 53.21 <0.001


A (Total)
B (Total)
AB (Total)
O (Total)

1802 (88) 142 (65)

OR (95% CI)


0.69 (0.230.21)



64 (44) 1.71 (1.212.40)

54 (37) 1.71 (1.222.40)




10 (7)

2.17 (1.114.27)




12 (8)
11 (7)

0.67 (0.371.21)
0.76 (0.411.41)



1 (1)

0.32 (0.061.86)



4 (4)

1.74 (0.644.74)



48 (33) 1.12 (0.781.60)

42 (29) 1.10 (0.761.60)



26 (23)
20 (18)

0.7 (0.451.09)
0.6 (0.370.98)





6 (5)

1.52 (0.663.50)




3 (2)

6 (4)

1.14 (0.502.61)

Note: POAG, primary open-angle glaucoma; PCAG, primary closed-angle glaucoma; PEXG, pseudoexfoliative glaucoma; OR, odds ratio.



6 (5)

1.89 (0.824.38)

47 (42) 1.61 (1.092.36)

43 (39) 1.6 (1.072.44)
4 (3)

ABO blood groups and glaucomaKhan et al.

rst gene associated with POAG, MYOC (TIGR/MYOC),
at the GLC1A locus was also on chromosome 1, encoding the protein myocilin. Interestingly, ABO blood group
genes are also present on chromosome 1.21 One explanation for the association of ABO blood groups could be
possible genegene interaction, as suggested by common
single nucleotide plolymorphisms in OLFM2 and OPTN
in glaucoma.22 ABO gene mutations associated with glaucoma may therefore provide insight into the relevance of
the ABO blood group in glaucoma. A second explanation could be differential gene expression in control and
glaucoma tissues. Comparison of gene expression proles of
normal and POAG trabecular meshwork revealed that the
trabecular meshwork in POAG tissues has a unique glycogene expression pattern that denes it as a group distinct
from normal.21 In addition, it cannot be discounted that
the ABO genes are in linkage disequilibrium with the glaucoma-associated genes. A different explanation could be the
involvement of differential glycosylation patterns; disorders
of glycosylation have been found to be frequently involved
in ocular and neurological abnormalities, including visual
eld loss and abnormal intraocular pressure, which are
characteristic of glaucoma.23,24 It has been shown previously
that the hallmark of these disorders is the depressed synthesis of certain oligosaccharide moieties of glycoproteins,
which is caused by defects in the genes coding for glycosyltransferases.25 The glycosyltransferase enzymes have also
been reported to regulate the expression of the carbohydrate
determinants of the ABO blood antigens.26 It may thus be
the case that glycosyltransferases, which are expressed in individuals with the B antigen, have some association with
glaucoma. Further studies are required to better understand
the underlying cause of this association.
The red blood cell Rh antigens have been implicated to be
important for the maintenance of red blood cell membrane
integrity.15,27,28 This integrity has been found to be altered in
POAG, as observed by changes in the acetylcholinesterase
activity.29 In the present study, a highly signicant association between Rh and POAG, as compared with controls,
was observed. This is consistent with the nding of Brooks
et al.,30 who reported a lower prevalence of Rh in chronic
closed-angle glaucoma. However, apart from this, no other
study has observed an association of the Rh blood group
with glaucoma. The difference in ndings could be due to
ethnicity or sample size. Our sample size is one of the largest reported to date. The association of Rh with POAG
may be due to the Rh antigens role in maintaining the
membrane integrity in POAG.25
In conclusion, an association between the B and Rh
blood groups has been found with POAG in patients of
Pakistani origin. Identication of future glaucoma genes is
of clinical signicance and has numerous commercial consequences, and would also lead to a better understanding
of the pathophysiology of the disease. It is worth pointing
out that a number of different genes have been shown to be
involved in the pathogenesis of glaucoma; in addition, en-

vironmental factors inuence the penetrance of the disease

and thus play a major role in the onset of glaucoma. Therefore, basing the diagnosis on only the blood group of an
individual will probably not have reliable prognostic value.
The authors wish to thank the administration of Al-Shifa Trust
Eye Hospital and the Christian Hospital Taxila for facilitating this
study. We would also like to thank all the subjects who volunteered their blood samples for this study. Funding for this work
was provided by the COMSATS Institute of Information Technology (to Muhammad Imran Khan). Part of the funding was
from the Shifa College of Medicine under a core grant to Raheel
Qamar. The authors have no proprietary or commercial interest
in any materials discussed in this article.

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Keywords: pseudoexfoliative glaucoma, angle-closure glaucoma,

open-angle glaucoma, Rh factors