Chemokine RANTES

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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)

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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.
  

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• 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-403A allele tended to associate with a
  higher risk of coronary artery disease (CAD) in
  Hungarian patients (Szalai et al. Atherosclerosis
  2001158233-39).
• In a LURIC (The Ludwigshafen Risk and
  Cardiovascular health) study in German population
  RANTES 403A allele was significantly associated
  with CAD (Simeoni et al. European Heart Journal
  2004 25,1438-46)

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AIMS

• To investigate whether RANTES promoter -403 G?A
  polymorphism is associated with myocardial
  infarction in the two Caucasian population
  (Czech, West-Slavonic Russian, East-Slavonic)
• In this case-control study to replicate the
  Hungarian and German studies in other
  populations.

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Study population

• Diagnosis of myocardial infarction was made
  according to standard international criteria.
• (Eur Heart J. 2000211502)

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RANTES promoter polymorphism genotyping and
statistical analysis

• RANTES -403 G/A polymorphism was genotyped by
  polymerase chain reaction with sequence specific
  primers (PCR-SSP)
• StatisticA 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
  Pearsons 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.

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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-403A allele was similar
  in control groups across several Caucasian
  populations (Figure 1)

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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 RANTES -403 G/A Czech population (N364) Czech population (N364) Russian population(N441) Russian population(N441)
RANTES -403 G/A RANTES -403 G/A MI (N224) Control (N140) MI (N244) Control (N197)
Genotype GG 69.5 65.7 63.5 67.0
Genotype GA 27.8 31.4 29.9 28.9
Genotype AA 2.7 2.9a 6.6 4.1a
Alleles G 83.0 81.4 78.5 81.5
Alleles A 16.5 18.5b 21.5 18.5b
A allele carriage A 30.5 34.3c 36.5 33.0c
a 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.
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Figure 1 Proportions of RANTES -403A allele in
patient with coronary artery disease and control
groups across selected populations
Czech republic, Olomouc Russian Federation (RF),
Novosibirsk myocardial infarction, data of
present study. Germanycoronary atherosclerosis,
Simeoni et al.,Eur Heart J.,2004251438. Hungary
coronary atherosclerosis, Szalai et al.,
Atherosclerosis.2001158233.
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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-403A 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 -403A 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.

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CONCLUSION

• The data do not support association between
  RANTES -403A 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.