Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk

Ghassibe-Sabbagh, Michella; Platt, Daniel E.; Youhanna, Sonia; Abchee, Antoine; Stewart, Krista J.; Badro, Danielle A.; Haber, Marc; Salloum, Angelique K.; Douaihy, Bouchra; Bayeh, Hamid el; Othman, Raed; Shasha, Nabil; Kibbani, Samer; Chammas, Elie; Milane, Aline; Nemr, Rita; Kamatani, Yoichiro; Hager, Jörg; Cazier, Jean‐Baptiste; Guyader, Dominique; Zalloua, Pierre

doi:10.1016/j.atherosclerosis.2012.02.035

Cited by 28 publications

(21 citation statements)

References 27 publications

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“…This negative correlation remained significant whether Hc plasma levels where ≥10 or ≥15, indicating a consistent threshold association. Given the correlation of T2DM and coronary artery disease (CAD), a previous study conducted on our study subjects showed an association of hyperhomocysteinemia with the degree of coronary artery stenosis in CAD patients [26]. …”

Section: Discussionmentioning

confidence: 99%

Type II diabetes mellitus and hyperhomocysteinemia: a complex interaction

Platt

Hariri

Salameh

et al. 2017

Diabetol Metab Syndr

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BackgroundElevated homocysteine (Hc) levels have a well-established and clear causal relationship to epithelial damage leading to coronary artery disease. Furthermore, it is strongly associated with other metabolic syndrome variables, such as hypertension, which is correlated with type II diabetes mellitus (T2DM). Studies on T2DM in relation to Hc levels have shown both positive and negative associations. The aim of the present study is to examine the relationship between Hc levels and risk of T2DM in the Lebanese population.MethodsWe sought to identify whether Hc associates positively or negatively with diabetes in a case–control study, where 2755 subjects enrolled from patients who had been catheterized for coronary artery diagnosis and treatment. We further sought to identify whether the gene variant MTHFR 667C>T is associated with T2DM, and how Hc and MTHFR 667C>T also impact other correlates of T2DM, including the widely used diuretics in this study population.ResultsWe found that Hc levels were significantly reduced among subjects with diabetes compared to those without diabetes when adjusted for all potential confounders (OR 0.640; 95% CI [0.44–0.92]; p = 0.0200). The associations between Hc levels and other variates contradicted the result: hypertension associates positively with high Hc levels, and with T2DM. The MTHFR 667C>T only associated significantly with high Hc levels.ConclusionThese results suggest population-specific variations among a range of mechanisms that modulate the association of Hc and T2DM, providing a probe for future studies.

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Section: Discussionmentioning

confidence: 99%

Type II diabetes mellitus and hyperhomocysteinemia: a complex interaction

Platt

Hariri

Salameh

et al. 2017

Diabetol Metab Syndr

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“…In 2008, Mager et al [24] reported that a 5.84-fold increase in risk of early CAD development was associated with the TT genotype of MTHFR rs1801133 polymorphisms among non-Oriental women compared to Ashkenazi women. Numerous studies have identified homozygotes for the T allele of rs1801133 in MTHFR as having fasting tHcy two times higher than homozygotes for the C allele [25]. However, another meta-analysis revealed no evidence for an increased risk of CAD in TT versus CC homozygotes for the MTHFR rs1801133 polymorphism [7].…”

Section: Discussionmentioning

confidence: 99%

OLR1,PON1andMTHFRGene Polymorphisms, Conventional Risk Factors and the Severity of Coronary Atherosclerosis in a Chinese Han Population

Liu

et al. 2013

Cell Physiol Biochem

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Aims: To explore the association between six single-nucleotide polymorphisms in OLR1, PON1, MTHFR gene and the angiographical characteristics of coronary atherosclerosis to determine if any of the conventional factors correlate with genetic polymorphisms in the advent of the disease. Methods: We examined rs1801131, rs1801133, rs3736232, rs3736234, rs854563 and rs662 by TaqMan® SNP Genotyping Assays in 1075 subjects that underwent angiography. The angiographical characteristics of coronary atherosclerosis were defined by the Gensini Score system. Results: The T allele of rs1801133 was associated with coronary atherosclerosis severity with the OR = 1.49, 95% CI = 1.04-2.14. In MTHFR gene, haplotype T-A was a susceptibility haplotype to coronary atherosclerosis (OR = 1.27, 95% CI = 1.06-1.51) whereas haplotype C-A had a protective effect (OR = 0.83, 95% CI = 0.70-0.99). In addition, several synergistic effects between rs1801133 and conventional risk factors such as diabetes and smoking were found. Conclusions: Collectively, the results demonstrate that the T allele of rs1801133 conferred an increased risk for coronary atherosclerosis. The MTHFR C-A haplotype was a protective haplotype, while T-A haplotype was a susceptibility haplotype. The presence of the T allele of rs1801133 increases the odds of coronary atherosclerosis severity when associated with conventional risk factors.

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“…Previous studies proved that MTHR polymorphisms elevate plasma homocysteine levels (21)(22)(23). On the other hand, statins cause small reductions (3.5%) in homocysteine blood concentrations (10).…”

Section: Discussionmentioning

confidence: 98%

Statin and MTHFR C677T Polymorphism in Patients with Cardiovascular Diseases

İzmirli¹,

Bacaksız²,

Alptekin³

et al. 2014

Bezmialem Science

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Objective: Cardiovascular disease (CVD) is the leading cause of death worldwide. The methylenetetrahydrofolate reductase (MTHFR) gene, located on the short (p) arm of chromosome 1 at position 36.3 (1p36.3), might be a possible risk factor for the pharmacogenetics in CVD. A common polymorphism in MTHFR (C677T, Ala→Val) decreases this enzyme activity and increases the homocysteine concentrations, predisposing one to heart disease. Alternatively, statins, cholesterol-reducing agents, are also used to reduce the homocysteine blood concentrations; the aim of the present study was to evaluate how the genotype frequencies of the MTHFR C677T polymorphism, namely rs1801133, change in the cardiovascular system in patients treated with statin. Methods:In this study, the genotype distribution of the MTHFR C677T polymorphism in CVD patients treated with statin (hydrophilic and lipophilic) (n=290) and healthy controls (n=151) was assessed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results:In this study, a statistically significant difference in genotype frequencies for the MTHFR C677T polymorphism was found between CVD patients treated with statin and controls (p=0.037). Yöntemler: Bu çalışmada, lipofilik ve hidrofilik statinler ile tedavi edilen kardiyovasküler sistem hastalarında (n=290) ve sağlıklı kontrollerde (n=151) MTHFR C677T polimorfizmindeki genotip dağılımları incelenmiştir. Genotipleme, Polimeraz zincir reaksiyonu (PCR) ve restriksiyon parça uzunluk polimorfizm (RFLP) yöntemi ile yapılmıştır. Bulgular: Bu çalışmada, MTHFR C677T polimorfizminin genotip dağılımında statin tedavisi gören kardiyovasküler sistem hastaları ile kontrol grubu arasında istatistiksel olarak anlamlı bir fark gözlenmiştir (p=0,037). ConclusionSonuç: Türk popülasyonunda statin ile tedavi edilen kardiyovasküler sistem hastaları ile MTHFR C677T polimorfizmi arasında istatistiksel olarak anlamlı bir ilişki ilk kez gösterilmiştir.

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Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk

Cited by 28 publications

References 27 publications

Type II diabetes mellitus and hyperhomocysteinemia: a complex interaction

Type II diabetes mellitus and hyperhomocysteinemia: a complex interaction

OLR1,PON1andMTHFRGene Polymorphisms, Conventional Risk Factors and the Severity of Coronary Atherosclerosis in a Chinese Han Population

Statin and MTHFR C677T Polymorphism in Patients with Cardiovascular Diseases

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