192 - Construction of Genetic risk score of 24 variants for coronary artery disease in the Pakistani subjects (ID 195)
Abstract
Background and Aims
Coronary artery disease (CAD) is the leading cause of mortality worldwide. Many conventional risk factors (CRFs), including age, gender, blood lipids, hypertension and smoking have been used routinely. The addition of genetic predisposition in the form of Genetic risk score (GRS) can discriminate better compared to use of CRFs alone. Current study analyzed genetic risk of CAD using a GRS of 24 SNPs and examined whether the GRS is associated with CAD and blood lipid levels.
Methods
465 (246 cases and 219 controls) subjects were genotyped for variants, NOS3rs1799983, SMAD3rs17228212, APOBrs1042031, LPArs3798220, LPArs10455872, SORT1rs646776, APOErs429358, GLULrs10911021, FTOrs9939609, MIA3rs17465637, CDKN2Ars10757274, DAB2IPrs7025486, CXCL12rs1746048, ACErs4341, APOA5rs662799, CETPrs708272, MRASrs9818870, LPLrs328, LPLrs1801177, PCSK9rs11591147, APOErs7412, PON1rs662, ITGB3rs5918, ALDH2rs671 and IL-6rs1800795 by various genotyping techniques. Blood lipids were measured using spectrophotometric methods.
Results
Individually, the risk allele frequencies were not significantly higher in cases than controls for most of the variants except MIA3, SMAD3, APoB, LPL and FTO variants. The single SNPs were not associated with CAD independently except MIA3, APoB, LPL and FTO variants. However, combined GRS of 24 SNPs was significantly higher in the cases than controls (16.93±3.19 vs 18.02±3.51, p=0.001) and was associated with CAD risk (OR 1.102, CI: 1.04-1.116, p=5.4×10-4). GRS showed significant association with increased TC and decreased HDl-C.
Conclusions
The GRS was quantitatively associated with CAD risk and showed association with some blood lipid levels. The inclusion of genetic information to CRFs while calculating the future risk of developing CAD can provide improved discrimination.
