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Objective: The study was to assess the knowledge and attitude of medical students and young medical college teachers regarding Genetic Risk Testing for Premature Coronary Artery Disease. Study Design: Cross Sectional Descriptive study. Setting: Azad Jammu and Kashmir Medical College, Muzaffarabad and Combined Military Hospital Muzaffarabad. Period: September, 2019 to December, 2019. Material & Methods: A self-completion online questionnaire was sent to collect the data from 298 medical students and 70 young medical college teachers (

Introduction: 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

Background Genetic information has the potential to create a more personalised, prompt, early and accurate risk evaluation. The effect of these genetic variants on the serum biomarker levels (phenotype) needs to be studied to assess their potential causal role in the pathogenesis of premature coronary artery disease (PCAD). Objectives were to determine the genotypic distribution of interleukin (IL) 18, tumour necrosis factor-α (TNFA), IL6 and IL10 single nucleotide polymorphisms (SNPs) in Pakistani PCAD cases and disease free controls and to study the effect of these gene polymorphisms on the serum cytokine levels (IL18, TNFA, IL6 and IL10) and cytokine imbalance (IL18:IL10 and TNFA:IL10). Material and methods The case–control study was carried out 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 assay. Results The risk allele frequencies (RAFs) of rs1800795 (IL6) and rs187238 (IL18) cytokine gene promoter SNPs were significantly higher in the PCAD cases as compared with the controls. Serum IL18 and IL10 levels were significantly greater in the IL18 rs187238 GG genotype patients while serum IL18 and IL6 levels were significantly higher in patients having the IL6 rs1800795 CC genotype. IL18 SNP rs1946519 significantly altered the IL18, TNFA, IL6, IL18/IL10 and TNFA/IL10 ratio levels followed by TNFA SNP rs1800629 which significantly altered the serum levels of IL18, IL18:IL-0 and TNFA:IL10 ratios. Conclusions 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.

Objectives: Interleukin-6 receptor (IL-6R) gene (A>C, rs8192284) polymorphismhas been associated with inflammatory biomarkers. We sought to investigate the association ofIL-6R gene (A>C, rs8192284) polymorphism with IL-6, IL-18 and hS-CRP levels in PCAD. StudyDesign: Case control study. Setting: Army Medical College, National University of Sciencesand Technology, Islamabad, Pakistan Methods: Total 520 subjects were recruited. 281 PCADpatients aged ≤45 years with >70% stenosis in at least one major coronary vessel along with239 age and sex matched controls were recruited. IL-6R polymorphism was determined byTaqMan genotyping while IL-6 and IL-18 levels were measured using ELISA technique and hSCRPon Immulite 2000. Results: The genotype distribution of IL-6R(rs8192284) in the cases andcontrols was: AA-56%(n=143);AC-36% (n=102); and CC-13% (n=36) and AA-59%(n=139);AC-33% (n=80); CC-8% (n=20) respectively. The risk allele frequency was significantly differentbetween the cases and controls (p=0.038) .IL-6 levels were significantly high (p

Background Premature Coronary Artery Disease (PCAD) 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. Moreover, the differential serum cytokine levels (IL-18 , IL-10 , IL-6 , TNF-alpha , IL-18:IL-10 & TNF-alpha:IL-10 ratios) with respect to the genotypic distribution of these selected SNPs were determined. Material and methods The case-control study was carried out 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 significantly 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 TNF-alpha, IL-10 and TNF-alpha:IL-10 ratio. It was followed by APOE rs7412 and CXCL12 rs1746048 which significantly altered the serum levels of IL-18; TNF-alpha and IL-18; IL-18:IL-10 ratio respectively. The cytokine imbalance denoted by IL-18:IL-10 was significantly higher in the risk allele carriers MIA3 rs17465637 and CXCL12 rs1746048 while TNF-alpha:IL-10 ratio was significantly raised 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.

Introduction: The objective was to evaluate diagnostic accuracy of high sensitivity C-reactive protein (hS CRP), Interleukin-18 (IL-18), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-10 (IL- 10), IL-18/IL- 10 ratio and their serum cut off values for identification of Premature Coronary Artery Disease (PCAD) patients. Method: It was a diagnostic validation case-control study carried out at the Clinical Pathology Laboratories of the Army Medical College, Rawalpindi, Pakistan, from May, 2013 to Jan, 2014. Two hundred and fifty subjects aged 70% stenosis, in at least one coronary vessel on angiography, were labeled to have PCAD. An equal number of angio-negative subjects were taken as controls from the study group. Serum IL- 10, IL- 18 and TNF alpha were measured using Enzyme Linked Immuno-sorbent Assay (ELISA), hS CRP on Immulite 1000 and serum cholesterol, Triglycerides and High Density Lipoprotein (HDL) by colorimetric methods. Statistical analysis was done using SPSS-17 and MedCalc software. Results: Total 196 subjects consisting of 98 PCAD patients and 98 angio-negative controls participated in the study. Mean ± SD age of PCAD patients was 40.7 ± 4.23yrs (89 males and 9 females) while in controls it was 35.1 ± 7.55yrs (93 males and 5 females). Serum hS CRP had highest area under curve AUC (95% confidence interval) of 0.936 (0.89- 0.97) while AUC (95% CI) of IL-18, TNF alpha and IL-10 were 0.853 (0.79-0.90), 0.731 (0.659-0.796) and 0.574 (0.497- 0.649) respectively. Sensitivity-specificity of hS CRP and IL-18 at cut off value of 3.18 pg/ml and 200pg/ml were 86%-91% and 77%-81% respectively while that of IL-18/IL-10 ratio and IL-10 at cut off values > 138.9 and > 0.3pg/ml were 68-64% and 20-100% respectively. Significant correlation was observed between hS CRP (p < 0.01), IL- 18 (p < 0.01) and TNF alpha (p < 0.05). Conclusion: hS CRP and IL-18 have the best diagnostic potential among the cytokines for detection of PCAD with high sensitivity and specificity. IL-18/IL-10 ratio had moderate significance in the diagnosis of PCAD although it correlated well with the disease burden. IL-10 had 100% specificity highlighting its role in the diagnosis of the disease but its low sensitivity is a limiting factor. Thus, hS CRP and IL-18 are promising potential biochemical parameters aiding in the clinical diagnosis of Premature Coronary Artery Disease.