Transcript Chemokine RANTES –403 G/A polymorphism in two Slavonic

Chemokine RANTES –403 G/A
polymorphism in two Slavonic
populations with myocardial
infarction
Tereshchenko IP 1,2, Petrkova J2,3, Mrazek F2,
Navratilova Z2, Lukl J3, Voevoda MI1, Petrek M2
1Institute
of Internal Medicine, RAMS Novosibirsk, Russia;
2Immunogenetics and 3Internal Medicine I, Palacky University
Olomouc, Czech Republic
(The study was supported by Czech government (ME-856). I.T. is recipient of
Visegrad fund fellowship)
Atherosclerosis & Inflammation
& Genetics
• Inflammation of coronary artery wall is a
critical process in the pathogenesis of
myocardial infarction (MI).
• MI is thought to have important genetic
component.
• The chemokine RANTES/CCL5 activates
and attracts T-lymphocytes to the sites of
ongoing inflammation.
• RANTES gene is a candidate for MI
susceptibility.
RANTES variants & Myocardial Infarction
• A single nucleotide polymorphism SNP locates at the
position -403 of the RANTES gene promoter (Guanin
by Adenin -403 G→A)
• RANTES-403*A allele tended to associate with a
higher risk of coronary artery disease (CAD) in
Hungarian patients (Szalai et al. Atherosclerosis 2001;158:233-39).
• In a LURIC (The Ludwigshafen Risk and
Cardiovascular health) study in German population
RANTES 403*A allele was significantly associated
with CAD (Simeoni et al. European Heart Journal 2004; 25,1438-46)
AIMS
• To investigate whether RANTES promoter
-403 G→A polymorphism is associated
with myocardial infarction in the two
Caucasian population (Czech, WestSlavonic; Russian, East-Slavonic)
• In this case-control study to replicate the
Hungarian and German studies in other
populations.
Study population
Slavonic
population
West-Slavonic
East-Slavonic
Czech
Russian
140
224
patients with MI
unrelated
healthy
controls
197
244
patients with MI
unrelated
healthy
controls
Diagnosis of myocardial infarction was made
according to standard international criteria.
(Eur Heart J. 2000;21:1502)
RANTES promoter polymorphism
genotyping and statistical analysis
• RANTES -403 G/A polymorphism was
genotyped by polymerase chain reaction with
sequence specific primers (PCR-SSP)
• Statistic:A statistical calculations were
performed using the SPSS v.13.0 (SPSS Inc,
Chicago, IL) The distribution of the RANTES
genotypes and alleles were analyzed using the
Pearson’s 2x2 contingency table 2-test and
odds ratios and 95% confidence interval (CI)
were estimated. The control populations was
tested for conformity to the Hardy-Weinberg
equilibrium.
RESULTS
• There were no significant differences in
RANTES -403 G/A genotype, allelic and
phenotype (carriage) frequencies between MI
patients and controls for both populations (Table
1)
• No differences after subgroup analysis (male /
female and age at 1st MI episode) was found.
• The proportion of RANTES-403*A allele was
similar in control groups across several
Caucasian populations (Figure 1)
Table 1: Genotype, allele and phenotype (carriage rates) frequencies of the
RANTES -403 G/A polymorphism in the groups of patients with myocardial
infarction and control subjects (in two investigated population)
RANTES
-403 G/A
Genotype
%
Alleles
%
A allele
carriage %
a
Czech population (N=364)
Russian population(N=441)
MI
(N=224)
MI
(N=244)
Control
(N=140)
Control
(N=197)
GG
69.5
65.7
63.5
67.0
GA
27.8
31.4
29.9
28.9
AA
2.7
2.9a
6.6
4.1a
G
83.0
81.4
78.5
81.5
A
16.5
18.5b
21.5
18.5b
A
30.5
34.3c
36.5
33.0c
p value for genotype: Czech – 0.75, Russian – 0.48; b p value for alleles: Czech – 0.49, Russian –
0.27; c p value for A allele carriage: Czech – 0.45, Russian – 0.46.
Figure 1: Proportions of RANTES -403*A allele in patient
with coronary artery disease and control groups across
selected populations
25
20
21,5
20,8
20
17,3
18,5
16,5
16,4
18,5
15
10
5
0
Germany
Hungary
Czech Rep.
patients
RF
control
Czech republic, Olomouc; Russian Federation (RF), Novosibirsk: myocardial
infarction, data of present study.
Germany:coronary atherosclerosis, Simeoni et al.,Eur Heart J.,2004;25:1438.
Hungary:coronary atherosclerosis, Szalai et al., Atherosclerosis.2001;158:233.
DISCUSSION
• The population size of Hungary cohort (Szalai et al,2001) and our
investigated two Slavonic population was identical. However,
genotype and alleles frequencies RANTES G-403*A distributed
not equally between two populations.
• Distribution of genotypes in LURIC study deviated significantly
from the expected in Hardy-Weinberg equilibrium. In this study
were performed statistical tests that do not assume HWE and
RANTES -403*A allele was significantly associated with CAD
(Simeoni et al., 2004). Our estimated groups are limits for the numbers
of participants but populations were strong compliance with the
HWE. Thus, technical genotyping errors are not the cause for
present discrepancies.
• Our pilot study, performed in cases and controls of Slavonic
ethnic origin, did not confirm this findings.
CONCLUSION
• The data do not support association
between RANTES -403*A allele and MI as
reported from LURIC (LUdwigshafen Risk
and Cardiovascular health) and Hungarian
cohort
• At least in Slavonic population, RANTES
promoter -403 G/A polymorphism does not
contribute to genetic determination of MI.