Genome-Wide Association Study in a Lebanese Cohort Confirms PHACTR1 as a Major Determinant of Coronary Artery Stenosis

Hager, Jörg; Kamatani, Yoichiro; Cazier, Jean‐Baptiste; Youhanna, Sonia; Ghassibe-Sabbagh, Michella; Platt, Daniel E.; Abchee, Antoine; Romanos, Jihane; Khazen, Georges; Othman, Raed; Badro, Danielle A.; Haber, Marc; Salloum, Angelique K.; Douaihy, Bouchra; Shasha, Nabil; Kabbani, Samer; Sbeite, Hana; Chammas, Elie; Bayeh, Hamid el; Rousseau, Francis; Zélénika, Diana; Gut, Ivo; Lathrop, Mark; Farrall, Martin; Guyader, Dominique; Zalloua, Pierre

doi:10.1371/journal.pone.0038663

Cited by 54 publications

(48 citation statements)

References 33 publications

(51 reference statements)

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“…This result is similar to that reported by Beaudoin et al [16], who performed electrophoretic mobility shift assays (EMSA) with HUVEC nuclear extracts and demonstrated the interaction between the rs9349379 polymorphism and the MEF2 factor. A GWAS performed in a Lebanese study recently confirmed the association of the PHACTR1 (rs9349379) gene polymorphism with coronary artery stenosis [5]. We agree with this report, since our data confirmed that the rs9349379 polymorphism is associated with premature CAD in a Mexican population.…”

Section: Discussionsupporting

confidence: 91%

PHACTR1 Gene Polymorphism Is Associated with Increased Risk of Developing Premature Coronary Artery Disease in Mexican Population

Pérez-Hernández

Vargas‐Alarcón

Posadas-Sánchez

et al. 2016

IJERPH

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Single-nucleotide polymorphisms (SNPs) in the protein phosphatase and actin regulator 1 gene (PHACTR1) have been associated with susceptibility to develop several diseases, including cardiovascular disease. The purpose of this study was to evaluate the role of two polymorphisms (rs2026458 and rs9349379) of the PHACTR1 gene in the susceptibility to the risk of developing premature coronary artery disease (CAD) in the Mexican population. The genotype analysis was performed using 5’exonuclease TaqMan genotyping assays in a group of 994 patients with premature CAD and 703 controls. A similar genotype distribution of rs2026458 was observed in both groups; however, under an additive model adjusted by age, body mass index, type 2 diabetes mellitus, smoking, dyslipidemia, and hypertension, the rs9349379 G allele was associated with a higher risk for developing premature CAD (odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.03–1.46, p-value (p) = 0.024). The two PHACTR1 polymorphisms were not in linkage disequilibrium. In summary, our results suggest that the PHACTR1 rs9349379 polymorphism plays an important role in the risk of developing premature CAD in the Mexican population.

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Section: Discussionsupporting

confidence: 91%

PHACTR1 Gene Polymorphism Is Associated with Increased Risk of Developing Premature Coronary Artery Disease in Mexican Population

Pérez-Hernández

Vargas‐Alarcón

Posadas-Sánchez

et al. 2016

IJERPH

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“…Detailed clinical and demographic information have been previously described [2] (Additional file 1). 406 out of the 991 participants had >50% stenosis in at least one vessel and were designated as severe CAD patients, 207 had stenosis ≤50% in at least one vessel and were designated as moderate CAD patients, and 378 had 0% stenosis and were classified as controls.…”

Section: Methodsmentioning

confidence: 99%

Multivariate epidemiologic analysis of type 2 diabetes mellitus risks in the Lebanese population

Ghassibe-Sabbagh

Deeb

Salloum

et al. 2014

Diabetol Metab Syndr

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BackgroundThe burden of diabetes in Lebanon requires well-targeted interventions for screening type 2 diabetes mellitus (T2DM) and prediabetes and prevention of risk factors. Newly recruited 998 Lebanese individuals, in addition to 7,292 already available, were studied to investigate the prevalence of diabetes, prediabetes and their associated risk factors.MethodsParticipants had fasting blood sugar and glycohemoglobin tests in addition to a lipid profile. Clinical and demographic information were obtained from a detailed questionnaire. The relationship between T2DM, its risk factors, and its complications were tested. Comparisons of these risk factors among diabetics, healthy, and coronary artery disease (CAD) patients were performed.ResultsThe prevalence of T2DM significantly increased with increasing BMI (p < 0.0001). Exercise activity level negatively correlated with the disease (p = 0.002), whereas the prevalence of T2DM (p < 0.0001) and CAD family history (p = 0.006) positively correlated with the affection status. The mean levels of triglycerides and LDL-C were significantly higher in diabetics (1.87; 1.35) compared to individuals with prediabetes (1.63; 1.26) and unaffected controls (1.49; 1.19). People with T2DM showed a significant decrease in HDL-C levels. A strong correlation of overall hyperlipidemia with the diabetes affection status was shown (p < 0.0001). Other comorbid factors such as hypertension (p < 0.0001) and self-reported obesity (p < 0.0001) were highly associated with T2DM and prediabetes. Reproductive health of women showed a strong correlation between giving birth to a baby with a high weight and the occurrence of T2DM and prediabetes later in life (p < 0.0001). Retinopathy and peripheral neuropathy were significantly correlated with diabetes and prediabetes (p < 0.0001).ConclusionsThe present study shows an alarming prevalence of diabetes and prediabetes in the studied subgroups representative of the Lebanese population.Electronic supplementary materialThe online version of this article (doi:10.1186/1758-5996-6-89) contains supplementary material, which is available to authorized users.

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“…This finding was replicated for association with various forms of coronary artery disease [2, 3] and ischemic stroke [4]. It has also shown significant association with coronary artery calcification, which is a major risk factor for coronary artery disease [5].…”

Section: Introductionmentioning

confidence: 81%

“…Several further studies have confirmed its association with coronary artery disease [3, 8–10] and coronary artery calcification [7, 11]. Due to strong linkage disequilibrium with rs12526453 SNP on the haplotype level, the associations of rs9349379 may be extended to rs12526453.…”

Section: Introductionmentioning

confidence: 98%

The rs12526453 Polymorphism in an Intron of the PHACTR1 Gene and Its Association with 5-Year Mortality of Patients with Myocardial Infarction

et al. 2015

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ObjectiveThe rs12526453 (C/G) is a single nucleotide polymorphism in an intron of the PHACTR1 gene (phosphatase and actin regulator 1). The C allele is associated with increased risk of coronary artery disease in an unknown mechanism. We investigated its association with long-term overall mortality in patients with ST-elevation myocardial infarction (STEMI) treated invasively.MethodsTwo independent groups of patients with STEMI were analyzed: a derivation group (n= 638) and a validation one (n=348). Genotyping was performed with the TaqMan method. The analyzed end-point was total long term mortality. Additionally, transcriptomic analysis was performed in mononuclear blood leukocytes from rs12526453 CC monozygotes or G allele carriers.ResultsIn the study group (mean age 62.3 ± 11.9 years; 24.9% of females, n=159), percentages of CC, CG, and GG genotypes were 45.3% (n=289), 44.7% (n=285), and 10% (n=64), respectively. In the 5-year follow-up 105 patients died (16.46%). CC homozygotes had significantly lower mortality compared to other genotypes: 13.1% (n=38) vs. 18.3% in G-allele carriers (n=67), (p=0.017, Cox`s F test). In the validation group 47 patients died within 3 years (13.5%). We confirmed lower mortality of CC homozygotes: 10.1 % (n=18) vs. 16.95% in G-allele carriers (n=29), (p=0.031, Cox`s F test). Transcriptomic analysis revealed a markedly higher expression of NLRP-2 in CC homozygotes.ConclusionsThe rs12526453 CC homozygotes (previously associated with increased risk of myocardial infarction) showed, in 2 independent samples, better long-term survival. The finding of such high effect size, after appropriate validation, could potentially be translated into clinical practice.

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Genome-Wide Association Study in a Lebanese Cohort Confirms PHACTR1 as a Major Determinant of Coronary Artery Stenosis

Cited by 54 publications

References 33 publications

PHACTR1 Gene Polymorphism Is Associated with Increased Risk of Developing Premature Coronary Artery Disease in Mexican Population

PHACTR1 Gene Polymorphism Is Associated with Increased Risk of Developing Premature Coronary Artery Disease in Mexican Population

Multivariate epidemiologic analysis of type 2 diabetes mellitus risks in the Lebanese population

The rs12526453 Polymorphism in an Intron of the PHACTR1 Gene and Its Association with 5-Year Mortality of Patients with Myocardial Infarction

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