Introduction: Genetic information which is specific to an individual has thepotential to improve Coronary Artery Disease (CAD) risk prediction. 13 CAD risk SNPs wereselected by removing SNPs in loci which had not been identified in CARDIoGRAMplusC4DGWAS. Linkage disequilibrium patterns differ between ethnic groups pointing towards theneed to investigate how the gene score would perform in different populations which is stilllargely unknown. Objective of the study was to investigate whether the 13 SNP CAD risk genescore has a role in the risk prediction of Pakistani Premature Coronary Artery Disease (CAD)cases and controls and to compare the CAD risk allele frequency between Pakistanis andCaucasians (samples obtained from the Northwick Park Heart Study II). Study Design: Casecontrolstudy. Setting: Army Medical College, National University of Sciences and Technology(NUST) in collaboration with the Cardiovascular Genetics Institute, University College London,UK. Materials and Methods: Total of 650 subjects with a history of chest pain were selected bynon-probability convenience sampling. Out of these subjects with > 70% stenosis in at least 1coronary vessel on angiography were labelled as Premature coronary Artery disease (PCAD)cases (n=340). The 13 SNPs were genotyped in a Pakistani case-control study (n=340 CADcases, 310 controls) using KASPar and Taqman assays. The use of 13 SNP gene score wastested in the prospective Northwick Park Heart Study (NPHSII) of 2775 healthy UK men (284cases) and the Pakistani case-control study subjects (n=650). Results: Mean ± SD age ofCAD patients was 42.7±3.80yrs while in controls it was 39.0±7.8yrs. Complete genotypingwas obtained for 635 samples (333 cases, 302 controls). The mean 13 SNP gene score wassignificantly higher in cases compared to controls (p=0.044). Odds ratio for CAD for eachquintile of 13 SNPs gene score showed a trend for higher quintiles of gene score to haveincreased odds ratio for CAD (p-value for trend=0.01) especially after adjusting for age, sexand ethnicity. There was a significant difference in risk allele frequency between Pakistanis andCaucasians (NPHSII) for all CAD risk SNPs except rs599839 (SORT1) (p=0.08). Conclusion:A 13 SNP gene score has significant potential role at differentiating between Pakistani PCADcases and controls. Risk allele frequencies for CAD differ significantly between Pakistanis andCaucasians stressing the need to develop population specific gene score keeping in view theethnic stratification.
A Genomewide Linkage Study of 1,933 Families Affected by Premature Coronary Artery Disease: The British Heart Foundation (BHF) Family Heart Study
