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Abstract Background The role of gene-environment interactions as risk factors for coronary heart disease (CAD) remains largely undefined. Such interactions may involve gene mutations and disease conditions such as type 2 diabetes mellitus (DM2) predisposing individuals to acquiring the disease. Methods In the present study, we assessed the possible interactive effect of DM2 and E-selectin S128R polymorphism with respect to its predisposing individuals to CAD, using as a study model a population of 1,112 patients and 427 angiographed controls of Saudi origin. E-selectin genotyping was accomplished by polymerase chain reaction (PCR) amplification followed by PstI restriction enzyme digestion. Results The results show that DM2 is an independent risk factor for CAD. In the absence of DM2, the presence of the R mutant allele alone is not significantly associated with CAD (p = 0.431, OR 1.28). In contrast, in the presence of DM2 and the S allele, the likelihood of an individual acquiring CAD is significant (odds ratio = 5.44; p = < 0.001). This effect of DM2 becomes remarkably greater in the presence of the mutant 128R allele, as can be observed from the odds ratio of their interaction term (odds ratio = 6.11; p = < 0.001). Conclusion Our findings indicate therefore that the risk of acquiring CAD in patients with DM2 increases significantly in the presence of the 128R mutant allele of the E-selectin gene.

Abstract Background The E-selectin p. S128R (g. A561C) polymorphism has been associated with the presence of angiographic coronary artery disease (CAD) in some populations, but no data is currently available on its association with CAD in Arabs. Methods In the present study, we determined the potential relevance of the E-selectin S128R polymorphism for severe CAD and its associated risk factors among Arabs. We genotyped Saudi Arabs for this polymorphism by PCR, followed by restriction enzyme digestion. Results The polymorphism was determined in 556 angiographically confirmed severe CAD patients and 237 control subjects with no CAD as established angiographically (CON). Frequencies of the S/S, S/R and R/R genotypes were found as 81.1%, 16.6% and 2.3% in CAD patients and 87.8%, 11.8%, and 0.4% in CON subjects, respectively. The frequency of the mutant 128R allele was higher among CAD patients compared to CON group (11% vs. 6%; odds ratio = 1.76; 95% CI 1.14 – 2.72; p = .007), thus indicating a significant association of the 128R allele with CAD among our population. However, the stepwise logistic regression for the 128R allele and different CAD risk factors showed no significant association. Conclusion Among the Saudi population, The E-selectin p. S128R (g. A561C) polymorphism was associated with angiographic CAD in Univariate analysis, but lost its association in multivariate analysis.

Abstract Background The association of the deletion in GSTT1 and GSTM1 genes with coronary artery disease (CAD) among smokers is controversial. In addition, no such investigation has previously been conducted among Arabs. Methods We genotyped 1054 CAD patients and 762 controls for GSTT1 and GSTM1 deletion by multiplex polymerase chain reaction. Both CAD and controls were Saudi Arabs. Results In the control group (n = 762), 82.3% had the T wild M wildgenotype, 9% had the Twild M null, 2.4% had the Tnull M wild and 6.3% had the Tnull M null genotype. Among the CAD group (n = 1054), 29.5% had the Twild M wild genotype, 26.6% (p < .001) had the Twild M null, 8.3% (p < .001) had the Tnull M wild and 35.6% (p < .001) had the Tnull M null genotype, indicating a significant association of the Twild M null, Tnull M wild and Tnull M null genotypes with CAD. Univariate analysis also showed that smoking, age, hypercholesterolemia and hypertriglyceridemia, diabetes mellitus, family history of CAD, hypertension and obesity are all associated with CAD, whereas gender and myocardial infarction are not. Binary logistic regression for smoking and genotypes indicated that only M null and Tnullare interacting with smoking. However, further subgroup analysis stratifying the data by smoking status suggested that genotype-smoking interactions have no effect on the development of CAD. Conclusion GSTT1 and GSTM1 null-genotypes are risk factor for CAD independent of genotype-smoking interaction.

Abstract Background The role of the Beta2-adrenoceptor (beta2-AR) Gln27Glu polymorphism in the manifestation of cardiovascular diseases is still unclear. Methods In the present study, we evaluated the potential relevance of the c.79 C>G (p.Gln27Glu) polymorphism of this receptor gene for coronary artery disease (CAD) and its associated risk factors in Saudi Arabs. Genotyping was performed by PCR using the confronting two-pair primer (PCR-CTPP) method. Results In the general population group (BD) (n = 895), 68.5% were homozygous wild-type C/C, 28.3% were heterozygous C/G and 3.2% were homozygous mutant G/G. Among the CAD patients (n = 773), 50.6% were homozygous wild-type C/C, 43.6% were heterozygous C/G and 5.8% were homozygous mutant G/G, while in the angiographed control group (CON) (n = 528), 71.8% were C/C, 24.4% C/G and 3.8% G/G genotypes. These results indicate that both the C/G (p = < .001) and G/G (p = .005) genotypes are significantly associated with CAD, when compared to the CON group. In addition, C/G (p = < .001) and G/G (p = < .001) were significantly associated with CAD, when compared to the BD group. Furthermore, stepwise logistic regression showed that the genotype [C/G (p < .001) and G/G (p < .001)] increase the risk of CAD. Conclusion These results shows that the Gln27Glu genotypes (homo- or heterozygous) of the beta2-AR may be independent predictors of severe CAD.

Presents an abstract of the article "Absence of Association Between Gln72Glu Polymorphism in the Beta-2-adrenergic Receptor Gene and CAD or CAD Risk Factors in Arabs," by Khaled Abu-Amero, O. Al-Boudari, and N. Dzmiri.

The GATA2 is a multi-catalytic transcription factor believed to play an important role in regulating inflammatory processes, largely contributory to cardiovascular-related events. However, its role in coronary artery disease (CAD) risk traits remains poorly understood. In a preliminary study using Affymetrix 250K, we established a link on chromosome (chr) 3, which harbors the GATA2 gene, to early onset of CAD in two families with heterozygous familial hyperlipidemia (HFH), suggesting a role for the gene in metabolic-related CAD in the general population. We then sequenced the gene in the families and an additional 200 individuals in the general population, followed by an association study for 8 SNPs on CAD metabolic risk traits in a total of 4557 individuals (2386 CAD cases versus 2171 angiographed controls) by the Applied Biosystems real-time PCR system. The rs1573949&#95;C [1.15(1.00-1.32); p=0.049] was associated with MI, rs7431368&#95;AA [5.2(1.05-26.60); p=0.43] conferred risk for harboring low high density lipoprotein, and obesity was linked to rs10934857&#95;AA [5.69(1.04-30.98); p=0.045] following Bonferroni corrections and multivariate adjustments for confounders. Furthermore, a haplotype CCCGGGTC (χ(2)=4.23; p=0.04) constructed from the eight studied SNPs and its 6-mer derivative CGGGTC (χ(2)=5.05; p=0.025) were associated with CAD. Obesity was associated with the 6-mer CATAAA (χ(2)=3.66; p=0.049), and hypercholesterolemia was linked to the 8-mer CCTGGACC (χ(2)=6.02; p=0.014), but most significantly so with its 5-mer derivative, CTGGA (χ(2)=6.75; p=0.009). On the other hand, high low density lipoprotein was linked to TGG (χ(2)=4.48; p=0.034). Our study points to an association of GATA2 at both SNP and haplotype levels with important metabolic risk traits for atherosclerosis., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We evaluated the role of the MEF2A as a risk factor for coronary artery disease (CAD) in 1186 subjects with angiographically documented disease compared with 885 CAD-free individuals in the Saudi population. Screening the gene revealed exon 11 as the most polymorphic of all coding regions, harbouring several substitution polymorphisms and insertion/deletions (indels) at a locus containing an 11 CAG trinucleotide chain and a CCGCCGCCA sequence, which introduced frameshifts and premature stop codons at nt146637 and nt146647, nt146780 or nt146783. While these indels were not significantly associated with CAD, a causative relationship was established for rs1059759 G>C [1.21(1.02-1.43); p=0.029], and a borderline one for rs34851361 A>G [1.22(0.9-1.54); p=0.088]. Importantly, a haplotype 1A-2G-3G-4A-5C-6G-7G-8A constructed from the studied SNPs was also associated with CAD [6.39(0.93-43.75); p=0.0052]. These results identify MEF2A gene as a susceptibility gene for CAD.