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notassociatedwith coronaryarterydiseasein aBrazilianpopulation
Apolipoprotein B (apo B) is the major protein of the low-density
lipoprotein (LDL) and it is involved with the transportation and
metabolism of cholesterol . Single nucleotide polymorphisms
(SNPs) from the human apo B gene (APOB) have been associated
with the risk of Coronary Artery Disease (CAD) [2,3].
The g.2488CNT (rs693, XbaI) polymorphism of the exon 26 APOB
results in a silent mutation, whereas the polymorphic site g.4154GNA
(rs1042031, EcoRI) results in an amino acid change (Glu→Lys) in exon
29. Two new studies, one with large number of subjects  and other
with gallbladder cancer subjects  highlighted the relevance of these
SNPs. Association studies of these polymorphisms with CAD produced
controversial results [2–4,6]. Therefore, we decided to investigate the
association of both these SNPs in a Brazilian population with CAD as
defined by angiographic procedures.
Four hundred and two unrelated Euro-Brazilians subjects were
classified in 2 groups: CAD+ (presence of stenosis≥50% in any coronary
artery, n=254) and control (stenosisb50%, n=148). Both groups were
under antilipemic therapy and presented similar anthropometric char-
acteristics. The Duke index was applied to verify the severity of the CAD.
The lipid profile (total cholesterol, HDL-cholesterol, LDL-cholesterol and
triglycerides), apolipoprotein A (apo A) and apo B were measured by
standard automated procedures (Hitachi 912, Roche Diagnostics).
Genotyping was performed by PCR–RFLP using XbaI and EcoRI as
restriction enzymes and the digested amplicons resolved by 1.5% agarose
(range 25–78 years), prevalence of males 58.3% and 15.6% with type 2
diabetes in the CAD group. This study was approved by the Ethical
Committee of Research in Human Beings of the Clinical Hospital of the
Federal University of Paraná, Brazil.
The serum lipid profile, apo A, apo B and other risk factors
body mass index) did not differ significantly among the groups. All
frequencies were similar (Table 1) among the groups. No association
between genotypes or alleles was found with the variables analyzed
(multiple regression). The allele frequencies for both polymorphisms
were similar to those reported for a European population .
Comparingour resultswith thoseof other studies2 major points are
noteworthy. First, all the subjects involved in our study were evaluated
by angiography while in most other studies the criteria for absence of
CAD (control group) were less stringent such as clinical evaluation and
non-invasive procedures. Second, the ethnic composition of thestudied
populations in case-control studies is a factor that may lead to
contrasting results. To minimize such complications we selected a
larger sample exclusively of Euro-Brazilian subjects and the control
group was age- and sex-matched with the CAD + group. In conclusion,
our data indicates that the studied polymorphisms were not associated
with coronary artery disease in a Euro-Brazilian population.
 Segrest JP, Jones MK, De Loof H, Dashti N. Structure of apolipoprotein B-100 in low
density lipoproteins. J Lipid Res 2001;42:1346–67.
 Scartezini M, Zago MA, Chautard-Freire-Maia EA, et al. The X-X-/E+E+ genotype of
the XbaI/EcoRI polymorphisms of the apolipoprotein B gene as a marker of
coronary artery disease in a Brazilian sample. Braz J Med Biol Res 2003;36:369–75.
 Chiodini BD, Barlera S, Franzosi MG, et al. Apo B gene polymorphisms and coronary
artery disease: a meta-analysis. Atherosclerosis 2003;167:355–66.
 Benn M, Stene MC, Nordestgaard BG, et al. Common and rare alleles in
apolipoprotein B contribute to plasma levels of low-density lipoprotein cholesterol
in the general population. J Clin Endocrinol Metab 2008;93:1038–45.
 Pandey SN, SrivastavaA, Dixit M, Choudhuri G, Mittal B. Haplotype analysis of signal
peptide (insertion/deletion) and XbaI polymorphisms of the APOB gene in
gallbladder cancer. Liver Int 2007;27:1008–15.
 Cavalli SA, Hirata MH, Salazar LA, et al. Apolipoprotein B gene polymorphisms:
prevalence and impact on serum lipid concentrations in hypercholesterolemic
individuals from Brazil. Clin Chim Acta 2000;302:189–203.
 Renges HH, Peacock R, Dunning AM, Talmud P, Humphries SE. Genetic relationship
between the 3′VNTR and diallelic apolipoprotein B gene polymorphisms: haplotype
analysis in individuals of European and South Asian origin. Ann Hum Genet
Mauren Isfer Anghebem-Oliveira⁎
Caroline Luise Prochaska
Medical Pathology Department of the Federal University of Paraná,
R. Lothário Meissner, 632, 80210-170, Curitiba, Paraná, Brazil
⁎ Corresponding author. Tel./fax: +55 41 3254 5667.
E-mail address: firstname.lastname@example.org (M.I. Anghebem-Oliveira).
Costantino Ortiz Costantini
Cardiologic Hospital C. Costantini, Curitiba, Paraná, Brazil
Emanuel Maltempi de Souza
Fábio O. Pedrosa
BiochemistryandMolecularBiologyDepartmentof the Federal University
of Paraná, Curitiba, Paraná, Brazil
17 December 2008
Clinica Chimica Acta 403 (2009) 261
Genotype and allele frequencies of APOB polymorphisms in the absence (controls) or
presence of coronary artery disease (CAD+).
Polymorphism Controls n=148 CAD+ n=254
0.40 [0.36–0.44]T allele frequency
19.1 [0.16–0.23] A allele frequency(χ2) 0.951
Values of genotypes are n (%).
P: 2-tailed Fisher exact test or χ2test.
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