Gamal Mohamed

T null and M null genotypes of the glutathione S-transferase gene are risk factor for CAD independent of smoking

BackgroundThe 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.MethodsWe genotyped 1054 CAD patients and 762 controls for GSTT1 and GSTM1 deletion by multiplex polymerase chain reaction. Both CAD and controls were Saudi Arabs.ResultsIn 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.ConclusionGSTT1 and GSTM1 null-genotypes are risk factor for CAD independent of genotype-smoking interaction.

Weak or no association of TCF7L2 variants with Type 2 diabetes risk in an Arab population.

BackgroundThe rs7903146 and rs12255372 variants of TCF7L2 have been strongly associated with type 2 diabetes (T2D) risk in most populations studied to date. Meta-analysis of 27 different studies has resulted in a global OR of 1.46 [1.42–1.51] (rs7903146 variant). Thus far, despite a high incidence of T2D, the role of this variant in Arabs has not been established.MethodsWe performed a case-control association study using 522 Saudi T2D patients (WHO criteria), and 346 controls (age > 60; fasting plasma glucose < 7 mmol/L). Genotyping was performed by pyrosequencing. Statistical analyses were performed using SPSS version 13.0 for Windows (SPSS, Chicago, IL, USA).ResultsFor rs7903146, the T allele frequency of the cases (0.415) was not different from that observed in the controls (0.405). The crude odds ratio (OR) was 1.04 with a 95% CI of 0.86–1.27 (P = 0.675). For rs12255372, the T allele frequency of the cases (0.368) was not different from that observed in the controls (0.355). Retrospective power calculations based upon an OR of 1.46 reported in a comprehensive meta-analysis of TCF7L2 risk, indicated this study was sufficiently powered (96.92%; α = 0.05) to detect an effect of similar magnitude to that reported for rs7903146.ConclusionOur study is consistent with weak or no association of T2D in Arabs with the two TCF7L2 variants, however it cannot rule out an effect of other SNPs in this gene. Future studies in this population are required to confirm our findings and may indicate the presence of yet to be defined genetic risk factors for T2D.

Genetic Study of Saudi Diabetes (GSSD) : significant association of the KCNJ11 E23K polymorphism with type 2 diabetes

The E23K variant of KCNJ11 has been associated with type 2 diabetes (T2D) in several but not all populations studied. Thus far, despite a high incidence of T2D, the role of this variant in Arabs has not been established.

The Glu27 genotypes of the beta2-adrenergic receptor are predictors for severe coronary artery disease.

BackgroundThe role of the Beta2-adrenoceptor (beta2-AR) Gln27Glu polymorphism in the manifestation of cardiovascular diseases is still unclear.MethodsIn 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.ResultsIn 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.ConclusionThese results shows that the Gln27Glu genotypes (homo- or heterozygous) of the beta2-AR may be independent predictors of severe CAD.

E-selectin S128R polymorphism and severe coronary artery disease in Arabs.

BackgroundThe 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.MethodsIn 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.ResultsThe 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.ConclusionAmong 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.

The interactive role of type 2 diabetes mellitus and E-selectin S128R mutation on susceptibility to coronary heart disease

BackgroundThe 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.MethodsIn 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.ResultsThe 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).ConclusionOur 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.

Beta 3 Adrenergic Receptor Trp64Arg Polymorphism and Manifestation of Coronary Artery Disease in Arabs

The substitution of tryptophan (Trp) by arginine (Arg) at position 64 in the β3-adrenoceptor (β3-AR) gene has been associated with obesity, diabetes mellitus, and coronary artery disease (CAD). We have investigated whether the Trp64Arg polymorphism is associated with the manifestation of CAD or one of its important risk factors, such as obesity, diabetes mellitus, elevated cholesterol and triglyceride levels, or hypertension in the Arab population. All participating subjects were genotyped for this polymorphism using the polymerase chain reaction followed by enzymatic digestion and sequencing. In the angiographed normal control subjects (n=495), 90.3% were homozygous Trp/Trp, 9.5% were heterozygous Trp/Arg, and 0.2% were homozygous for the Arg/Arg genotype, compared to 87%, 12.3%, and 0.7%, respectively, among angiographically confirmed CAD patients (n=981). There was no statistical difference in the distribution of genotypes or allele frequencies between the CAD and control groups. We carried out a stepwise logistic regression analysis to study the possible combined effect of the genotypes and other risk factors on CAD. All variables were retained in the model, with p values of 0.014, 0.006, 0.005, <0.001, 0.045, 0.002, <0.001, and 0.016 for genotype, diabetes mellitus, sex, family history of CAD, obesity, myocardial infarction, smoking, and age, respectively. In conclusion, the Trp64Arg polymorphism of the β3-AR gene does not represent an independent risk factor for CAD in Arabs. However, in the presence of other CAD risk factors, this polymorphism may be used as a predictor of CAD.