Open AccessPREMATURE CORONARY ARTERY DISEASE
Author(s) -
Wafa Omer,
Amer Siddiq,
Omer Jamshed Khan,
Dilshad Ahmed Khan,
Ejaz Hassan Khan Khattak,
Abdul Khaliq Naveed
Publication year - 2018
Publication title -
the professional medical journal/the professional medical journal
Language(s) - English
Resource type - Journals
eISSN - 2071-7733
pISSN - 1024-8919
DOI - 10.29309/tpmj/2018.25.05.327
Subject(s) - medicine , single nucleotide polymorphism , coronary artery disease , snp , interleukin 10 , taqman , pathogenesis , cytokine , immunology , bioinformatics , gene , real time polymerase chain reaction , genetics , biology , genotype
Integrative genomics may help in the identification of novelbiological pathways in the pathogenesis of CAD. Objectives: To find out the association of 5Cytokine SNPs and 13 CAD SNPs gene risk scores with serum cytokine levels in PrematureCoronary Artery Disease (PCAD). To identify the direct and indirect protein interactions of the 13CAD risk genes and the 5 cytokine genes in PCAD. Study Design: Case-control study. Setting:Army Medical College, in association with University College London (UCL), London, UnitedKingdom (UK). Materials and Methods: 340 PCAD patients and 310 age and sex matchedcontrols were recruited. Serum IL18, TNFA, IL6 and IL10 levels were measured using ELISA(Invitrogen). The SNPs were genotyped using TAQMAN and KASPar assays. Data analysis wasdone using standard SPSS software version-21 (SPSS Inc, Chicago, Illinois, USA). The proteinproteininteraction (PPI) network was generated using STRING version 9.0, Genemania andI-Tessar web. Results: The patients of PCAD had mean ± SD age of 42 ± 3.80 years consistingof 329 males and 11 females. The 5 SNP cytokine gene risk score correlated significantly withthe serum IL-18, IL-6, TNF-alpha, IL-18: IL-10 and TNF-alpha: IL-10 ratios (p<0.01). The 13 CADSNP gene risk score also correlated significantly with the serum IL-18, TNF-alpha, IL-18: IL-10and TNF-alpha: IL-10 ratios but not with serum IL-6 levels. IL-6 works in close interaction withIL-6R, STAT3 and NFKB1. While MRAS, MIA3 and SORT1 interact with each other CXCL-12mediates its actions by interacting with IL-18, JAK-2 and CCR4. LPA interacts closely with APOBand LPL acts via interaction with APOA4 and APOA5. Conclusion: The correlation betweengene risk scores and serum cytokine levels can aid in the analysis of complex networks tounderstand the pathogenesis of PCAD.