Association of the angiotensinogen gene polymorphism with atherosclerosis and its risk traits in the Saudi population

BACKGROUND: Angiotensinogen (AGT) constitutes a central component of the renin-angiotensin system that controls the systemic blood pressure and several other cardiovascular functions and may play an important role in atherosclerosis pathways. In this study, we employed TaqMan genotyping assays to evaluate the role of 8 AGT variants in primary hypertension (HTN), type 2 diabetes mellitus (T2DM), and obesity as a possible trigger of coronary artery disease (CAD) in a population of 4615 angiographed native Saudi individuals. METHODS: Linkage analysis was done by using the Affymetrix Gene Chip array, sequencing by using the MegaBACE DNA analysis system and genotyping accomplished by TaqMan chemistry using the Applied Biosystem real-time Prism 7900HT Sequence Detection System. RESULTS: Six variants, rs2067853 GG [Odds ratio(95% Confidence Interval) = 1.44(1.17-1.78); p = 0.001], rs7079 [1.49(1.20-1.85); p < 0.0001], rs699 G [1.19(1.08-1.13); p < 0.0001], rs3789679 A [1.51(1.14-1.99); p = 0.004], rs2148582 GG [1.31(1.11-1.55); p = 0.002] and rs5051 TC + CC [1.32(1.13-1.60); p = 0.001] conferred risk for HTN (3521 cases versus 1094 controls). The rs2067853 (p = 0.042), rs699G (p = 0.007) and rs5051 (p = 0.051) also conferred risk for myocardial infarction (MI; 2982 vs 1633), while rs3789679 A (p < 0.0001) and GA + AA (p < 0.0001) as well as rs4762G (p = 0.019) were associated with obesity (1576 vs 2458). However, while these variants appeared to be also associated with CAD (2323 vs 2292), only the rs7079G (p = 0.035) retained its significant relationship. Interestingly, among the haplotypes constructed from these SNPs, the baseline 8-mer haplotype, GGTGGGGT (χ(2) = 7.02; p = 0.0081) and another GGCGGAGT (χ(2) = 5.10; p = 0.024), together with several of their derivatives were associated with HTN. T2DM was associated with two 8-mer haplotypes, GGTAGGAC (χ(2) = 5.66; p = 0.017) and ATTGAGAC (χ(2) = 5.93; p = 0.015), obesity with GGCGGAGT (χ(2) = 9.49; p = 0.0021) and MI was linked to ATTGGGAC (χ(2) = 6.68; p = 0.010) and GGTGGGAT (χ(2) = 4.25; p = 0.039). Furthermore, several causative haplotypes were also shared among the risk traits as well as with CAD. CONCLUSION: These results point to AGT as independently conferring risk for various cardiovascular traits, and possibly interacting with these traits in events leading to atherosclerosis

Data on common variants associated with coronary artery disease/myocardial infarction in ethnic Arabs

The data shows results acquired in a large cohort of 5668 ethnic Arabs involved in a common variants association study for coronary artery disease (CAD) and myocardial infarction (MI) using the Affymetrix Axiom Genotyping platform (“A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs” Wakil et al. (2015) [1] ). Several loci were described that conferred risk for CAD or MI, some of which were validated in an independent set of samples. Principal Component (PCA) analysis suggested that the Saudi Cohort was close to the CEU and TSI populations, thus pointing to similarity with European populations

A New Susceptibility Locus for Myocardial Infarction, Hypertension, Type 2 Diabetes Mellitus, and Dyslipidemia on Chromosome 12q24

We examined the role of hepatic nuclear factor-1 alpha (HNF1a) gene polymorphism on coronary artery disease (CAD) traits in 4631 Saudi angiographed individuals (2419 CAD versus 2212 controls) using TaqMan assay on ABI Prism 7900HT sequence detection system. Following adjustment for confounders, the rs2259820_CC (1.19 (1.01–1.42); P=0.041), rs2464196_TT (1.19 (1.00–1.40); P=0.045), and rs2259816_T (1.13 (1.01–1.26); P=0.031) were associated with MI. The rs2259820_T (1.14 (1.03–1.26); P=0.011) and rs2464196_C (1.12 (1.02–1.24); P=0.024) were associated with type 2 diabetes mellitus (T2DM), while the rs2393791_T (1.14 (1.01–1.28); P=0.032), rs7310409_G (1.16 (1.03–1.30); P=0.013), and rs2464196_AG+GG (1.25 (1.05–1.49); P=0.012) were implicated in hypertension. Hypertriglyceridemia was linked to the rs2393791_T (1.14 (1.02–1.27); P=0.018), rs7310409_G (1.12 (1.01–1.25); P=0.031), rs1169310_G (1.15 (1.04–1.28); P=0.010), and rs1169313_CT+TT (1.24 (1.06–1.45); P=0.008) and high low density lipoprotein-cholesterol levels were associated with rs2259820_T (1.23 (1.07–1.41); P=0.004), rs2464196_T (1.22 (1.06–1.39); P=0.004), and rs2259816_T (1.18 (1.02–1.36); P=0.023). A 7-mer haplotype CATATAC (χ2=7.50; P=0.0062), constructed from the studied SNPs, was associated with MI, and CATATA implicated in T2DM (χ2=3.94; P=0.047). Hypertriglyceridemia was linked to TGCGGG (χ2=4.26; P=0.039), and obesity to ACGGGT (χ2=5.04; P=0.025). Our results suggest that the HNF1a is a common susceptibility gene for MI, T2DM, hypertension, and dyslipidemia