BackgroundCoronary artery disease (CAD) is a major killer in today’s world. Pakistan is also affected by this non-communicable disease like other countries. It is a multifactorial disease and is influenced by many gene-gene and gene-environment interactions.MethodsA total of 623 (219 controls, 404 cases) Pakistani subjects were genotyped for four SNPs, rs662 (PON1), rs5918 (ITGB3), rs671 (ALDH2), rs1800795 (IL-6) by PCR-RFLP. Various anthropometric parameters were noted and serum lipid profile was measured using commercially available kits. Statistical analysis was done by SPSS version 22. A Genetic Risk Score (GRS) was calculated from individual SNPs. The association of the SNPs and the GRS with CAD was checked using logistic regression.ResultsThe results showed that the risk allele frequencies of all variants were higher in the cases than the controls, however the difference was not statistically significant association (p > 0.0125). The mean GRS in the controls was 3.99 ± 1.42 and in cases, it was 4.29 ± 1.39, the difference between the groups was significant (p = 0.0109). logistic regression of individual SNPs and GRS with the CAD showed that independent SNPs were not significantly associated with the CAD however, the GRS had a strong association (p = 1.4 × 10− 4). The subjects were divided into three groups based on GRS (Gp 1 with GRS 0–2, Gp 2 with GRS 3–5 and Gp 3 with GRS 6–8). The analysis of the effect of the individual SNPs and GRS groups on different lipid profile parameters revealed no significant association of any of the tested SNPs with any lipid parameter, however, the GRS groups showed marginally significant for TC and highly significant association for TG, LDL-c and HDL-c.ConclusionIn conclusion, use of a GRS can provide better information than individual SNPs. The larger the number of the SNPs included in the analysis, the better would be the risk prediction.

Background Diabetes mellitus is a multifactorial disorder characterized by a high level of glucose in the blood. Both genetic and environmental factors interact to cause diabetes. Insulin receptor substrate ( IRS ) proteins have a significant part in insulin signaling pathways. We aimed to investigate the relationship of type 2 diabetes with a Gly972Arg (G972R) variant of the IRS-1 gene and Gly1057Asp (G1057D) polymorphism of IRS-2 gene in the population of Punjab, Pakistan. Methods We collected 926 samples, 500 healthy controls (fasting blood sugar < 99 mg/dL, random blood sugar < 126 mg/dL) and 426 cases with diabetes (fasting blood sugar > 99 mg/dL, random blood sugar > 126 mg/dL). Several anthropometric measurements were measured. Statistical analysis was performed by using SPSS to determine the allele group/genotype frequency of the selected variants in the study population. Results The genotyping results of G972R by RLFP-PCR showed the allelic frequency of G = 0.68 and R = 0.32 in controls while G = 0.71 and R = 0.29 in the cases. The minor R allele had a slightly higher frequency in the cases than the controls (OR = 0.86, CI 0.706–1.052, p = 0.17). The genotyping results of G1057D showed allelic frequency G = 0.74 and D = 0.26 in the controls while G = 0.961 and D = 0.29 in the cases. The minor D allele appeared to be a risk allele for this SNP although the difference in the allele frequencies was not statistically significant (OR = 1.55, CI 0.961–1.41, p = 0.108). The combined genotype analysis showed that the difference in the allele and genotype frequencies reached statistical difference between the cases and the controls as well as the odds ratio substantially increased when the R allele (G972R) was present together with D allele (G1057D) in any combination. When the association of single variants with the lipid traits was observed, only D allele (G1057D) showed significant association with TG, HDL and LDL, however when the analysis was repeated for combined genotypes using general linear model, many more significant associations between the genotype where D allele and R allele are together, were seen with many lipid traits. Conclusion In conclusion, the single nucleotide polymorphisms with low-modest effect size may not affect the phenotype individually but when in combination, the effect becomes stronger and more visible, therefore, for the SNP association studies, the more the number of SNPs included in the analysis, the more meaningful the results. Electronic supplementary material The online version of this article (10.1186/s13098-019-0459-1) contains supplementary material, which is available to authorized users.