ROLE OF THE APOB GENE POLYMORPHISM (c.12669G>A,
p.Gln4154Lys) IN CORONARY ARTERY DISEASE IN
THE INDIAN PUNJABI POPULATION Sharma R1,*, Mahajan M2, Singh B1, Singh G3, Singh P3 *Corresponding Author: Ritu Sharma, Department of Biochemistry, Government Medical College, Circular
Road, Amritsar-143001, Punjab, India; Tel.: +91-183-257-3637; Fax: +91-183-242-6506: E-mail: ritu_gmc@
rediffmail.com page: 35
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DISCUSSION
In the present study, the role of the APOB gene
polymorphism (c.12669G>A,p.Gln4154Lys) was studied in native Indian Punjabi subjects suffering
from CAD. Three APOB genotypes, i.e., R+R+, R+R–
and R–R– are possible. However, only two genotypes
R+R+ and R+R– were observed in both control subjects
and CAD patients in this study. The R–R– genotype
was not observed. The occurrence of this genotype
in other populations has been reported to vary
from infrequent to nil [23]. Frequency of the R– allele was observed to be high in CAD patients when compared
to control subjects in the population under study.
In other populations, increased frequency of the R– allele
has also been reported in CAD patients as compared
to normal subjects [8,9]. On the other hand, no
significant difference in the frequency of the R– allele
has been reported in South Asian CAD patients and
normal subjects living in Britain [10]. Similar results
have been reported in the Brazilian population [11].
Thus, the R– allele is not associated with CAD in all
the populations. In the Indian Punjabi population, the
R+R– genotype was more frequent in CAD patients
in comparison to control subjects and accordingly, the
frequency of the R– allele was higher in CAD patients.
This clearly indicates that the R– allele is associated
with increased susceptibility toward CAD development
in our population. In a study on the South Indian
Tamil population, the frequency of the R– allele has
been reported to be 0.054 [13], which is close to that
observed in our population (0.04). It may be noticed
that this comparison was done in a healthy population
only and it may be possible that frequency of the R–
allele would be more in the Tamil population suffering
from CAD. However, they have not reported this
data. No significant variations in lipid and lipoprotein
cholesterol levels in CAD patients having either the
R+R+ or R+R– genotype were observed. Similar results
have been reported in South Indian [13] and in
Brazilian populations [11]. Hegele et al. [8] also observed
no difference in total or LDL cholesterol levels
in CAD patients and normal subjects with different
apoB genotypes in the American population. However,
positive association of APOB gene EcoR1 polymorphism
with elevated lipid levels has been reported in
the Russian population [12]. In the present study, we
observed raised serum apoB levels in CAD patients
with the R+R– genotype as compared to those having
the R+R+ genotype. On the contrary, insignificant
difference in apoB levels of CAD patients with different
apoB genotypes has been reported in the American
population. In the Indian population from the city of
Lucknow, Uttar Pradesh, India, higher levels of apoB
and LDL cholesterol were reported in CAD patients
with the R+R+ apoB genotype [24]. Thus, the relationship
between the R– allele of apoB and raised serum
apoB levels is not consistent in all populations and thus
need to be verified in different ethnic groups.
Raised serum apoB levels were associated with
the R– allele in our population. It seemed interesting
to investigate if this APOB gene polymorphism could
affect the heterogeneity of LDL particles and its oxidation.
However, no significant difference was observed
in MDA-LDL levels and apoB carbonyl content in
CAD patients having the R+R+ and R+R– genotypes,
thereby indicating that this APOB gene polymorphism
does not affect the LDL oxidation status in the Indian
Punjabi population. Independent of the genotype, both
MDA-LDL levels and apoB carbonyl content were
raised in CAD patients in comparison to control subjects.
Similar results were observed when Log triglyceride/
HDL-C values were compared in CAD patients
having the R+R+ or R+R– APOB genotypes. An increased
susceptibility of LDL to oxidation has been reported
in CAD patients by other investigators [25,26].
Overall, CAD patients had increased predominance of
small dense LDL particles that are more prone to oxidation.
However, this observation was independent of
APOB genotype. This clearly indicates that some other
factors such as environment or nutrition might be more
potent in bringing structural and functional changes in
apoB of LDL.
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