Decoding the role of NOS3 rs1799983 and PON1 rs662 variants in cardiovascular diseases

Abstract

Background Cardiovascular diseases (CVDs) are complex diseases determined by various environmental risk factors and genetic susceptibility, and NOS3 and PON1 are considered one of the susceptible genes for CVD. Our study aims to evaluate the association of NOS3 rs1799983 and PON1 rs662 variants with CVD. Methods A case–control study was conducted among equal number (252) of cases and controls in the Pakistani population to investigate the significance of NOS3 (rs1799983) and PON1 (rs662) variants in causing CVD risk. Genotyping was performed using Tetra-ARMS PCR to evaluate the genotype–phenotype correlation. For meta-analysis, the case–control studies of NOS3 rs1799983 and PON1 (rs662) variants and CVD were included by searching various databases according to PRISMA guideline. Eligible data were extracted and pooled and were analyzed using Review Manager version 5.4 based on four different genetic models. Results Our case–control study showed that both NOS3 rs1799983 (OR = 2.39, p = < 0.0001, AIC value = 710.50) and PON1 rs662 (OR = 7.30, p = < 0.0001, AIC value = 680.10) variants significantly increase the risk of CVD under recessive genetic contrast model. The meta-analysis of NOS3 rs1799983 showed association with CVD under all four genetic model's understudy, however, no heterogeneity was found under recessive model only. Meta-analysis for PON1 rs662 showed association with homozygous genetic contrast model only, whereas heterogeneity was observed under all the genetic model's understudy. Conclusions We found NOS3 rs1799983 was associated with the increased risk of CVD under four genetic contrast models, while PON1 rs662 polymorphisms associated with homozygous genetic contrast model in different populations only. These results can be utilized to identify individuals at high risk of CVDs and for disease management.