PREMATURE CORONARY ARTERY DISEASE

POTENTIAL ROLE OF A 13 SNP GENE RISK SCORE IN THE RISK PREDICTION OF PAKISTANI PATIENTS

Abstract

Introduction: Genetic information which is specific to an individual has the
potential to improve Coronary Artery Disease (CAD) risk prediction. 13 CAD risk SNPs were
selected by removing SNPs in loci which had not been identified in CARDIoGRAMplusC4D
GWAS. Linkage disequilibrium patterns differ between ethnic groups pointing towards the
need to investigate how the gene score would perform in different populations which is still
largely unknown. Objective of the study was to investigate whether the 13 SNP CAD risk gene
score 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 and
Caucasians (samples obtained from the Northwick Park Heart Study II). Study Design: Casecontrol
study. 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 by
non-probability convenience sampling. Out of these subjects with > 70% stenosis in at least 1
coronary 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 CAD
cases, 310 controls) using KASPar and Taqman assays. The use of 13 SNP gene score was
tested in the prospective Northwick Park Heart Study (NPHSII) of 2775 healthy UK men (284
cases) and the Pakistani case-control study subjects (n=650). Results: Mean ± SD age of
CAD patients was 42.7±3.80yrs while in controls it was 39.0±7.8yrs. Complete genotyping
was obtained for 635 samples (333 cases, 302 controls). The mean 13 SNP gene score was
significantly higher in cases compared to controls (p=0.044). Odds ratio for CAD for each
quintile of 13 SNPs gene score showed a trend for higher quintiles of gene score to have
increased odds ratio for CAD (p-value for trend=0.01) especially after adjusting for age, sex
and ethnicity. There was a significant difference in risk allele frequency between Pakistanis and
Caucasians (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 PCAD
cases and controls. Risk allele frequencies for CAD differ significantly between Pakistanis and
Caucasians stressing the need to develop population specific gene score keeping in view the
ethnic stratification.