Association of β-Adrenergic Receptor Gene Polymorphisms With Acute Coronary Syndrome and Cardiovascular Risk Factors in an Arab Population

El‐Menyar, Ayman; Rizk, Nasser; Asim, Mohammad; Al-Thani, Hassan; Elgendy, Akram Y.; Al-Suwaidi, Jassim

doi:10.1177/0003319715618039

Cited by 9 publications

(3 citation statements)

References 36 publications

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“…The 5 nuclease assay was performed using 20 ng of genomic DNA, 1× TaqMan Universal PCR Master Mix (Applied Biosystems) and 1× primer/probe mix using the correct conditions for an extension by the manufacturer's instructions. Negative controls were used as previously described [22].…”

Section: Genotyping Of the Polymorphisms Of The Variants Rs4986790 Anmentioning

confidence: 99%

TLR4 Receptor D299G/T399I Haplotype Polymorphism Is Associated with Insulin Resistance in Obese Female Subjects

Sharif

Alwakeel

Mohamed

et al. 2020

Genes

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Background: Activation of Toll-like-receptor 4 (TLR4) causes chronic inflammation that can result in obesity and metabolic syndrome (MeS). Aim: This study aimed to investigate the role of TLR4 polymorphisms of TLR4D299G/T399I, and its impact on protein expression of TLR4 in obese female subjects. Methodology: A prospective cross-sectional association study was performed on Arab female subjects from Qatar University. The subjects were categorized according to BMI classifications into two groups: “obese; n = 69” and “non-obese; n = 136”. Anthropometric measurements, weight (kg), height (m) and waist circumference (WC) were evaluated, and the body mass index (BMI) was calculated. Fasting blood samples were collected, and assessment of glucose, lipid profile, C-reactive protein (CRP), leptin, IL-6 and insulin was performed. Insulin resistance was computed using HOMA-IR. Genotyping of the TLR4 polymorphisms of TLR4D299G (rs4986790) and TLR4T399I (rs4986791) was performed by the 5′ nuclease assay by TaqMan MGB probe. Flow cytometry was used to evaluate the monocyte cell surface expression of TLR4. Results: The frequency distribution of the genotype revealed that homozygous AA is the most frequent among obese subjects (86.4%) for (TLR4D299G, A > G) and the homozygous CC genotype is the most frequent (92.4%) for (TLR4T399I, C > T). Haplotype analysis of TLR4 D299G/T399I showed that GT carriers had a significant association with increased probability of insulin resistance (odds ratio = 4.73; 95% CI 1.19–18.90; p-value = 0.016). The monocyte cell surface of TLR4 was significantly higher by 1.3 folds in obese compared to non-obese subjects. Conclusions: TLR4 D299G/T399I haplotype polymorphism is associated with an increased risk of insulin resistance with the upregulation of TLR4 protein expression in obese subjects.

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Section: Genotyping Of the Polymorphisms Of The Variants Rs4986790 Anmentioning

confidence: 99%

TLR4 Receptor D299G/T399I Haplotype Polymorphism Is Associated with Insulin Resistance in Obese Female Subjects

Sharif

Alwakeel

Mohamed

et al. 2020

Genes

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“…The ADRB2 gene encodes the β2-adrenoreceptor, which plays a vital role in regulating the cardiovascular system ( Dai et al, 2021 ). Several SNPs in the ADRB2 gene could impact cardiovascular activity, thereby altering the risk of hypertension ( El-Menyar et al, 2015 ; Huang et al, 2018 ). Nielsen and colleagues found that carriers of the minor allele (G) showed a tendency toward vasodilation and high cardiac output during anesthesia.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine

Ding,

Liu,

Wang

et al. 2023

Front. Genet.

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Introduction: Dexmedetomidine (DXM) is widely used as an adjuvant to anesthesia or a sedative medicine, and differences in individual sensitivity to the drug exist. This study aimed to investigate the effect of genetic polymorphisms on these differences.Methods: A total of 112 patients undergoing hand surgery were recruited. DXM 0.5 μg/kg was administered within 10 min and then continuously injected (0.4 μg/kg/h). Narcotrend index, effective dose and onset time of sedation, MAP, and HR were measured. Forty-five single nucleotide polymorphisms (SNPs) were selected for genotype.Results: We observed individual differences in the sedation and hemodynamics induced by DXM. ABCG2 rs2231142, CYP2D6 rs16947, WBP2NL rs5758550, KATP rs141294036, KCNMB1 rs11739136, KCNMA1 rs16934182, ABCC9 rs11046209, ADRA2A rs1800544, and ADRB2 rs1042713 were shown to cause statistically significant (p < 0.05) influence on the individual variation of DXM on sedation and hemodynamics. Moreover, the multiple linear regression analysis indicated sex, BMI, and ADRA2A rs1800544 are statistically related to the effective dose of DXM sedation.Discussion: The evidence suggests that the nine SNPs involved in transport proteins, metabolic enzymes, and target proteins of DXM could explain the individual variability in the sedative and hemodynamic effects of DXM. Therefore, with SNP genotyping, these results could guide personalized medication and promote clinical and surgical management.

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“…Little is known about the genetic basis of CHD in the ME. 18,19 Prior GWAS in ME populations failed to replicate several known CHD loci. [20][21][22] To address this gap in knowledge, we initiated the Qatar Cardiovascular Biorepository in 2014 to collect DNA and plasma of CHD cases and controls, with the goal of studying the "omics" of CHD in Qatari individuals.…”

mentioning

confidence: 99%

Validation of Polygenic Risk Scores for Coronary Heart Disease in a Middle Eastern Cohort Using Whole Genome Sequencing

Saad

El‐Menyar

Kunji

et al. 2022

Circ: Genomic and Precision Medicine

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Background: Enthusiasm for using polygenic risk scores (PRSs) in clinical practice is tempered by concerns about their portability to diverse ancestry groups, thus motivating genome-wide association studies in non-European ancestry cohorts. Methods: We conducted a genome-wide association studies for coronary heart disease in a Middle Eastern cohort using whole genome sequencing and assessed the performance of 6 existing PRSs developed with methods such as LDpred (PGS000296), metaGRS (PGS000018), Pruning and Thresholding (PGS000337), and an EnsemblePRS we developed. Additionally, we evaluated the burden of rare variants in lipid genes in cases and controls. Whole genome sequencing at 30× coverage was performed in 1067 coronary heart disease cases (mean age=59 years; 70.3% males) and 6170 controls (mean age=40 years; 43.5% males). Results: The majority of PRSs performed well; odds ratio (OR) per 1 SD increase (OR 1sd ) was highest for PGS000337 (OR 1sd =1.81, 95% CI [1.66–1.98], P =3.07×10 −41 ). EnsemblePRS performed better than individual PRSs (OR 1sd =1.8, 95% CI [1.66–1.96], P =5.89×10 −44 ). The OR for the 10th decile versus the remaining deciles was >3.2 for PGS000337, PGS000296, PGS000018, and reached 4.58 for EnsemblePRS. Of 400 known genome-wide association studies loci, 33 replicated at P <10 −4 . However, the 9p21 locus did not replicate. Six suggestive ( P <10 −5 ) new loci/genes with plausible biological function were identified (eg, CORO7 , RBM47 , and PDE4D ). The burden of rare functional variants in LDLR , APOB , PCSK9 , and ANGPTL4 was greater in cases than controls. Conclusions: Overall, we demonstrate that PRSs derived from European ancestry genome-wide association studies performed well in a Middle Eastern cohort, suggesting these could be used in the clinical setting while ancestry-specific PRSs are developed.

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Association of β-Adrenergic Receptor Gene Polymorphisms With Acute Coronary Syndrome and Cardiovascular Risk Factors in an Arab Population

Cited by 9 publications

References 36 publications

TLR4 Receptor D299G/T399I Haplotype Polymorphism Is Associated with Insulin Resistance in Obese Female Subjects

TLR4 Receptor D299G/T399I Haplotype Polymorphism Is Associated with Insulin Resistance in Obese Female Subjects

Genetic polymorphisms are associated with individual susceptibility to dexmedetomidine

Validation of Polygenic Risk Scores for Coronary Heart Disease in a Middle Eastern Cohort Using Whole Genome Sequencing

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