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J Med Oncl Ther 2017 | Volume 2 Issue 4
Oncology and Biomarkers Summit
November 27-28, 2017 | Atlanta, USA
Annual Congress on
Background:
Coronary Artery Disease (CAD) occurs almost
a decade earlier in the South Asian population as compared
to the West. Inclusion of genetic information can prove to
be a robust measure to improve early risk prediction of
PCAD. Aim was to estimate the genotypic distribution and
risk allele frequencies of 13 Coronary Artery Disease (CAD)
risk Single Nucleotide Polymorphisms in loci identified
by the CARDIoGRAMplusC4D consortium namely MIA3
rs17465637;9p21 rs10757274; CXCL12 rs1746048; APOA5
rs662799; APOB rs1042031; LPA rs3798220; LPA 10455872;
MRAS rs9818870; LPL rs328; SORT1 rs646776; PCSK9
rs11591147; APOE rs429358; APOE rs7412 in Pakistani PCAD
patients and controls and to determine the differential
serum cytokine levels (IL18,IL10,IL6, TNFalpha, IL18:IL10
& TNFalpha:IL10 ratios) with respect to the genotypic
distribution of these selected SNPs.
Material & Methods:
The study design was case-control
and it was conducted in National University of Sciences
and Technology, Islamabad in collaboration with the
Cardiovascular Genetics Institute, University College London,
UK. Subjects (n=340) with >70% stenosis in at least a single
major coronary artery on angiography were taken as PCAD
cases along with 310 angiographically verified controls.
ELISA was performed for measuring the concentrations of
serum IL18, TNFA, IL6 and IL10. Genotyping was done using
TAQMAN and KASPar assays.
Results:
The risk allele frequencies (RAF) of APOE rs7412,
CXCL12 rs1746048, 9p21 rs10757274, MIA3 rs17465637 and
SORT1 rs646776 were markedly higher in the PCAD cases as
compared to the controls. APOE rs429358 had the greatest
influence among the selected GWAS/CARDIoGRAMplusC4D
consortium CAD risk SNPs by significantly altering the serum
levels of TNFalpha, IL10 and TNFalpha:IL10 ratio followed
by APOE rs7412 and CXCL12 rs1746048 which significantly
altered the serum levels of IL18; TNFalpha and IL18;
IL18:IL10 ratio respectively. The cytokine imbalance denoted
by IL18:IL10 was statistically significantly greater in the risk
allele carriers MIA3 rs17465637 and CXCL12 rs1746048
while TNFalpha:IL10 ratio was raised markedly in the risk
allele carriers of APOE rs429358; MRAS rs9818870 and LPL
rs328.
Conclusion:
The association of the selected SNPs with
differential serum cytokine levels especially the cytokine
imbalance points towards their potential causal role in the
immune inflammatory pathogenic pathway of PCAD.
e:
wafamuniransari@gmail.comEffect of coronary artery disease risk SNPS on serum cytokine levels and cytokine imbalance in premature
coronary artery disease
Wafa M Ansari
National University of Science and Technology, Pakistan