Polymorphisms of MTHFR, eNOS, ACE, AGT, ApoE, PON1, PDE4D, and Ischemic Stroke: Meta-Analysis

Wei, Loo Keat; Au, Anthony; Menon, Shruti; Griffiths, Lyn R.; Kooi, Cheah Wee; Looi, Irene; Zhao, Jianping; Lee, Chaeyoung; Alekseevna, Avdonina Maria; Hassan, Muhammad; Aziz, Zariah Abdul

doi:10.1016/j.jstrokecerebrovasdis.2017.05.048

Cited by 72 publications

(68 citation statements)

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“…NO is an indispensable reactive species which is mainly generated by inducible NOS enzyme in pathologic conditions, particularly in ischaemic stroke. Moreover, it has been suggested that genetic polymorphisms of NOS have a significant relationship with the pathophysiological processes of ischaemic stroke . The production of considerable amounts of NO in ischaemic tissues may cause neuronal damage by reacting with superoxide anion which causes the formation of peroxynitrite.…”

Section: Discussionsupporting

confidence: 90%

Attenuating effect of α-pinene on neurobehavioural deficit, oxidative damage and inflammatory response following focal ischaemic stroke in rat

Khoshnazar

Bigdeli

Parvardeh

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives Oxidative stress and inflammation have a critical role in the pathogenesis of ischaemic stroke. Alpha‐pinene is a monoterpenoid molecule with anti‐inflammatory and antioxidant properties. The nobility of the present study was to evaluate the neuroprotective effect of α‐pinene in ischaemic stroke. Methods Ischaemic stroke was induced by transient middle cerebral artery occlusion followed by 24 h reperfusion in male Wistar rats. Alpha‐pinene (25, 50 and 100 mg/kg, i.p.) was administered in the beginning of reperfusion. Then, the neurobehavioural function, infarct volume, brain oedema, antioxidant enzyme activity and the concentration of malondialdehyde (MDA), nitric oxide (NO) and interleukin‐6 (IL‐6) were evaluated by different methods in the brain. Key findings Alpha‐pinene (50 and 100 mg/kg) elicited a significant decrease in the brain oedema and infarct size as well as an improvement in the neurobehavioural function. Besides, α‐pinene (100 mg/kg) restored the function of superoxide dismutase, catalase and glutathione peroxidase and reduced the concentration of MDA, NO and IL‐6 in the hippocampus, cortex and striatum. Conclusions It was ultimately attainted that α‐pinene exerts neuroprotective effect in ischaemic stroke in rat through the restoration of antioxidant enzymes activity, attenuation of lipid peroxidation and reduction of inflammation in the ischaemic brains.

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Section: Discussionsupporting

confidence: 90%

Attenuating effect of α-pinene on neurobehavioural deficit, oxidative damage and inflammatory response following focal ischaemic stroke in rat

Khoshnazar

Bigdeli

Parvardeh

et al. 2019

Journal of Pharmacy and Pharmacology

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“…As for MTHFR A1298C , our studies found no significant association of MTHFR A1298C genotypes and the risk or severity of CAD in this Chinese Han population. Earlier literature focuses mainly on its association with the risk of ischemic stroke [30], but there is no convincing evidence of a link to the risk of CAD.Based on our data, we postulated that the mutations of MTHFR might increase the risk and aggravate the severity of CAD, possibly by hindering homocysteine recycling, but related basic mechanisms need to be further clarified.…”

Section: Discussionmentioning

confidence: 69%

A Case-Control Study of the Association of the Polymorphisms of MTHFR and APOE with Risk Factors and the Severity of Coronary Artery Disease

et al. 2019

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Objectives: To explore the association between single-nucleotide polymorphisms (SNPs) in MTHFR and APOE and the risk of CAD and, more importantly, the severity of CAD and the profile of serum lipids, we performed a case-control study in a Chinese Han population. Methods: A total of 1,207 cases of consecutive CAD-suspected inpatients were recruited, and 406 CAD cases and 231 non-CAD controls were enrolled for the final analysis after screening for exclusion criteria. All subjects had undergone coronary angiography, and the severity of CAD was evaluated by 2 cardiologists according to the Gensini scores. The genotypes of MTHFR and APOEwere detected using real-time PCR, and then verified by Sanger sequencing. Environmental risk factors, such as age, sex, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia, and BMI were collected. Statistical analyses (the χ² test, binary logistic regression analysis, and ordinal polytomous logistic regression analysis) were performed with SPSS v16.0. Results: The genotypes ofall the subjects included in the CAD and non-CAD groups in this study were successfully detected, with an agreement of 100% with Sanger sequencing. The distributions of genotypes CT and TT at MTHFR C667T were higher in CAD cases than in non-CAD controls (OR 1.99, 95% CI 1.34–2.95; OR 1.77, 95% CI 1.18–2.67; p < 0.05), whereas genotype AC at MTHFR A1298Cwas lower in CAD cases (OR 0.71, 95% CI 0.50–1.02; p < 0.05). A significant association was observed in genotypes CT and TT at MTHFR C667T and the risk of CAD (OR 1.44, 95% CI 1.27–3.67; OR 1.56, 95% CI 0.88–2.78; p < 0.05). Both genotypes and alleles of APOE were comparable in the CAD cases and non-CAD controls (p > 0.05). The genotype TT at MTHFR C667T and ε4+ at APOE were more likely to be found in the CAD subgroup with a Gensini score ≥72 (p = 0.040 and p = 0.028, respectively). Meanwhile, in the patients with genotype TT,a higher level of serum Hcy was detected, while genotype ε4+ patients possessed higher levels of serum apolipoprotein E (ApoE) and low-density lipoprotein cholesterol (LDL-C) than other genotypes. Conclusion: This study revealed that the SNP site of MTHFR C667Tis associatedwith the risk of CAD in this Chinese Han population. In addition, the genotypes of TT in MTHFR C667T and ε4+in APOE may increase the severity of CAD, and higher Hcy, LDL-C, and ApoE levels may be involved in this pathogenic process.

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“…51 These 2 polymorphisms have been reported to convert susceptibility to multiple diseases in the central nervous system, including ischemic stroke, PD, MS, and so on. [52][53][54] However, their roles in migraine require further confirmation.…”

Section: Discussionmentioning

confidence: 99%

Effects of MTHFR C677T and A1298C Polymorphisms on Migraine Susceptibility: A Meta‐Analysis of 26 Studies

Liu

et al. 2019

Headache

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Background Multiple studies have evaluated the associations between 5,10‐methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and migraine risk with conflicting results. Therefore, we conducted a meta‐analysis on this theme. Methods We searched the electronic databases of PubMed, EmBase, ScienceDirect, and Cochrane Library for all relevant studies published until April 6, 2018. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) in allelic, dominant, recessive, homozygous, and heterozygous models were calculated using random effects model to assess the strength of associations. We also performed subgroup analyses stratified by ethnicity and migraine subtypes, respectively. Results Twenty‐six studies (20 in Caucasians, 3 in Asians, 2 in Indians, and 1 in Pakistanis) with 10,228 migraineurs and 28,608 controls were included in this meta‐analysis. In the overall population, the allele 677T and TT genotype were associated with an increased risk for total migraine and migraine with aura (MA) (total migraine: T vs C: OR = 1.19, 95%CI = 1.06‐1.33, P = .004; TT vs CC: OR = 1.32, 95%CI = 1.07‐1.64, P = .011; MA: T vs C: OR = 1.28, 95%CI = 1.09‐1.51, P = .003; TT vs CC: OR = 1.51, 95%CI = 1.09‐2.08, P = .012), but not for migraine without aura (MO). Subgroup analysis stratified by ethnicity revealed similar findings in Caucasians. In Asians, the association was detected only in recessive model in total migraine (TT vs CT + CC: OR = 1.80, 95%CI = 1.14‐2.85, P = .012). Results in Indians did not suggest any association in either total migraine or its subtypes. Pooled results of 5 studies (4 in Caucasians and 1 in Indians) on A1298C polymorphism indicated a significant association between the CC genotype and migraine risk (CC vs AA: OR = 1.78, 95%CI = 1.03‐3.07, P = .038), which only appeared for MO (CC vs AA: OR = 2.83, 95%CI = 1.30‐6.16, P = .009). Conclusions Our meta‐analysis suggested that allele 677T in MTHFR C677T polymorphism might be a genetic risk factor for MA in Caucasians, and genotype 1298CC might contribute to MO susceptibility.

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Polymorphisms of MTHFR, eNOS, ACE, AGT, ApoE, PON1, PDE4D, and Ischemic Stroke: Meta-Analysis

Cited by 72 publications

References 45 publications

Attenuating effect of α-pinene on neurobehavioural deficit, oxidative damage and inflammatory response following focal ischaemic stroke in rat

Attenuating effect of α-pinene on neurobehavioural deficit, oxidative damage and inflammatory response following focal ischaemic stroke in rat

A Case-Control Study of the Association of the Polymorphisms of <b><i>MTHFR</i></b> and <b><i>APOE</i></b> with Risk Factors and the Severity of Coronary Artery Disease

Effects of MTHFR C677T and A1298C Polymorphisms on Migraine Susceptibility: A Meta‐Analysis of 26 Studies

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