Association of ACE and NOS3 Gene Polymorphisms with Blood Pressure in a Case Control Study of Coronary Artery Disease in Punjab, Pakistan

Single nucleotide polymorphisms (SNPs), ACE rs4341 and NOS3 rs1799983 have been reported to be associated with coronary artery disease (CAD) and blood pressure (BP)in many but not all studies. We aimed to investigate the effect of these SNPs on BP and CAD in people from Punjab, Pakistan. A total of 650 subjects (430 CAD cases and 220 controls) were genotyped by TaqMan/KASPar allelic discrimination technique. Two BP measurements were reordered and their mean was calculated. The results showed that the risk allele frequencies (RAFs) of both SNPs were higher in cases than controls but the difference was not statistically significant. For rs4341, RAF in cases and controls was 0.577 vs. 0.525, p = 0.08 and for rs1799983, the RAF was 0.202 vs. 0.178, p = 0.31. The SNPs were not associated with CAD. The CAD odds ratio of rs4341 (1.22,0.97-1.53, p = 0.09) and that of rs1799983 (1.15, 0.86-1.54, p=0.33) was not statistically significant. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly higher in cases than controls (p<0.05) and the SNPs showed a significant association with BP. Each risk allele of rs4341 (G) increased SBP by 10.04±0.8 mmHg and DBP by 2.5±0.6mmHg, while risk allele of rs1799983 (T), increased SBP and DBP by 16.4±0.9mmHg and 8.8±0.6mmHg respectively, all were statistically significant (p<0.05). When a combined effect of genotypes of both SNPs was examined, a significant effect on CAD outcome (p=0.01) was observed when GG of rs4341 and GT of rs1799983 co-existed. Similarly, maximum elevation in BP was observed when risk alleles of both SNPs in homozygous form (GG and TT) appeared together. In conclusion, the SNPs were not independently associated with CAD but were associated with BP in Pakistani subjects under study and may be causing CAD by modulating BP.