A genetic association between Myocardial Infarction MI and Interleukin1 B 3953 gene polymorphism in

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A genetic association between Myocardial
Infarction (MI) and Interleukin-1 B ( 3953)
genepolymorphism in turkish population

• Ahmet Arman1, Ajda Coker2, Ozer Soylu3, Aydin
  Yildirim3 and Tuna Tezel3
• 1The Faculty of Engineering, 2The Department of
  Biology, Art and Sciences, Marmara University,
  Istanbul/Turkey, 3The Department of Cardiology,
  Dr. Siyami Ersek Hospital, Istanbul/Turkey.

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MYOCARDIAL INFARCTION

• Coronary artery disease
• occurs when the blood supply to to a part of the
  heart is interrupted
• oxygen shortage causes damage and potential death
  of heart tissue.

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Cross section of complete coronary artery
inclusion
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MYOCARDIAL INFARCTION

• Heart diseases major cause of
• Morbitiy
• Dead in USA, Europe and Turkey
• Aetiology and pathogenic mechanisms of coronary
  vessels diseases are not known very well, but
• Calssical risk factors
• Environmental Factors
• Genetics

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RISK FACTORS

• Classical risk factors
• Alder age, gender (male), smoking, hypertention,
  diabetes, obesity, lifestle, hypercholesterolemia
• New risk factors
• Fibrinogen, homocystein, lipoproteins, C-reactive
  protein (CRP), elevated levels of cytokines and
  interleukins

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GENETIC MARKERS

• Gene polymorphisms
• influence genetic expression of interleukins
• May be involved in protein activity
• May more informative in assesing the risk factors
• Some alleles of cytokines more frequently found
  than the control

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The role of inflammatory factors in pathogenesis
of atherosclerosis

• ? levels of vascular adhesion and Vascular
  permeability
• EC and SMC activation
• Protease induced plaque rupture

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Atherosclerosis Inflammation
Myocardial Infraction
Inflammation (IL-8, TNF, IL-1)
MI
Plaqe rupture
Fibrous Cap
Anti- Inflammatory Agents (IL-10, TGF-ß, IL-1Ra)
Fatty Streak

• oxLDL
• Mechanical Shear stress
• Viruses
• Toxins

Normal Artery
Normal Artery Wall
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Why some people susceptible to MI

• Human genome Project
• 3 of sequence in human is protein coding
  sequences
• 97 of sequence in genome is junk DNA
• Majority variations occur at junk DNA
• Is there any affect of polymorphisms on
  proinflammatory factors for protection or
  susceptibility to MI

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IL-1 FAMILY

• IL-1 ?
• IL-1 ?
• IL-1 Ra

Proinflammatory Agents
Anti-inflammatory Agent
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POLYMORPHISMS IN IL-1RN AND IL-1B GENES

• VNTR in IL-1RN gene
• Different number of repeating 86 basepair
  sequences
• is six alleles based on repeating 86 bp
• Single nucleotide polymorphism (SNP) in IL-1 ?
  gene
• -511 C/T
• 3953 C/T

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Methods

• Study Group
• MI with lt 40 70
• MI with gt 40 95
• The control 117
• Blood samples from MI and the control
• DNA isolation
• PCR
• Restriction Fragment Length Polymorphism

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RESULTS
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Genotyping of A)IL-1RN VNTR, B) IL-1B -511 (C/T)
and C) IL-1B 3953 (C/T) SNPs
1/3
2/2
1/2
1/2
1/1
1/1
2/2
1/2
2/2
1/1
M
M
M
304 bp
XV BCLF 2007
190 bp
249 bp 135 bp 114 bp
500 bp
114 bp
300 bp
200 bp
100 bp
A B
C
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Genotype distribution and allele frequency of
IL-1RN Gene VNTR Polymorfism in MIlt40 and control
groups
P lt0,05
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Genotype distribution and allele frequency of
IL-1RN Gene VNTR Polymorfism in MIgt40 and control
groups
P lt0,05
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Genotype distribution and allele frequency of
IL-1B Gene -511 polymorphism in MIlt40 and control
P lt0,05
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Genotype distribution and allele frequency of
IL-1B Gene -511 polymorphism in MIgt40 and control
P lt0,05
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Genotype distribution and allele frequency of
IL-1B Gene 3953 polymorphism in MIlt40 and control
OR 3,999, 95 CI 2,553-6,264
P lt0,05
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Genotype distribution and allele frequency of
IL-1B Gene 3953 polymorphism in MIgt40 and
control groups
OR 2,146, 95CI 1,418-3,248
P lt0,05
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Comparison of Genotype distribution and allele
frequency of IL-1B Gene 3953 polymorphism
between MIgt40 and MI lt40 groups
P lt0,05
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RESULTS

• There was no difference genotype distribution
  and allele frequence of IL-1RN and IL-1 B -511
  between MI lt40 and the controls or MIgt40 and the
  controls
• Signigicant association was seen in genotype
  ditribution and allele frequency of IL-1 B 3953
  between MIlt40 and the control or MIgt40 and the
  control

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CONCLUSION

• Patients with MI lt 40 carrying allele 2 of IL-1
  B 3953 have 4 times more likely to have had a
  heart attack than normal people (OR 3,999, 95
  CI 2,553-6,264)
• Patients with MI gt40 carrying allele 2 of IL-1 B
  3953 have 2 times more likely to have had a
  heart attack than normal people (OR 2,146,
  95CI 1,418-3,248)

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THANK YOU!!!!!