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: Case control 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
ABSTRACT
High-sensitivity C-reactive protein [hS-CRP] is an acute phase protein that is often used for the risk estimation of cardiovascular diseases. Objective was to find out the reference range of hS-CRP in the healthy adult northern Pakistani population and compare the distribution in relation with age, gender, body mass index [BMI], ethnicity and smoking. Cross-sectional study. Army Medical College Rawalpindi from Nov 2007 - Mar 2009 In this cross-sectional study a total of 297 healthy adults [>18 years] comprising 207 males, 90 females, Punjabis [n=178] and Pathans [n=119] were randomly included from Rawalpindi, Lahore, Peshawar and Sawabi Districts. History and clinical examination were carried out. Serum hS-CRP was analysed in Clinical Pathology Laboratory, Army Medical College Rawalpindi by two site sequential chemiluminiscent immunometric assay kit on immulite 1000 [USA]. Data were analysed by SPSS-16. The reference values for hS-CRP are presented as median [2.5 th - 97.5 th percentile]. In the healthy adult population of Northern Pakistan it was 1.84 mg/L [0.37-4.81] mg/l; in Punjabis 1.75 [0.30-4.65] mg/l and in Pathans 1.93 [0.50-5.30] mg/l. Females had higher hS-CRP levels 2.05 [0.53-5.66] mg/l as compared to the males 1.76 [0.31-5.06] mg/l. Smokers had relatively higher hS-CRP 1.98 mg/l [0.47-5.56] mg/l than non-smokers 1.68 mg/l [0.30-4.60]. Our data also revealed that hS-CRP had significant positive correlation with advancing age [r=0.20;p<0.05] and increasing BMI [r=0.29;p<0.01]. The reference range for hS-CRP in the population of Northern Pakistan is 0.37-4.81 mg/l. Pathans have higher hS-CRP levels than Punjabis. Demographic factors including age and BMI were positively correlated to the distribution of hS-CRP