Methylation Map Genes Can be Critical in Determining the Methylome of Intracranial Aneurysm Patients

Shafeeque, Chathathayil M.; Sathyan, Sanish; Saradalekshmi, Koramannil R; Premkumar, S.; Allapatt, Jacob P; Banerjee, Moinak

doi:10.2217/epi-2019-0280

Cited by 4 publications

(5 citation statements)

References 38 publications

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Section: Discussionmentioning

confidence: 99%

“…Preclinical evidence suggests a methionine-rich diet may correlate with an elevated risk and expedited formation of IA, 25 and specific genetic variants of the homocysteine cycle have been linked with an increased IA risk. 26,27 Retrospective studies offer contradictory results. 29 identified an association between homocysteine and IA patients [OR 2.2 (95%CI 1.19-4.06)], but both patients and controls exhibited exceptionally high homocysteine levels.…”

Section: Intracranial Aneurysmmentioning

confidence: 99%

See 1 more Smart Citation

Homocysteine serum levels in patients with ruptured and unruptured intracranial aneurysms: a case-control study

Mota Telles,

Rosi Junior,

Yamaki

et al. 2024

Arq Neuropsiquiatr

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Background There is very few data regarding homocysteine's influence on the formation and rupture of intracranial aneurysms. Objective To compare homocysteine levels between patients with ruptured and unruptured intracranial aneurysms, and to evaluate possible influences of this molecule on vasospasm and functional outcomes. Methods This is a retrospective, case-control study. We evaluated homocysteinemia differences between patients with ruptured and unruptured aneurysms; and the association of homocysteine levels with vasospasm and functional outcomes. Logistic regressions were performed. Results A total of 348 participants were included: 114 (32.8%) with previous aneurysm rupture and 234 (67.2%) with unruptured aneurysms. Median homocysteine was 10.75µmol/L (IQR = 4.59) in patients with ruptured aneurysms and 11.5µmol/L (IQR = 5.84) in patients with unruptured aneurysms. No significant association was detected between homocysteine levels and rupture status (OR = 0.99, 95% CI = 0.96-1.04). Neither mild (>15µmol/L; OR = 1.25, 95% CI 0.32-4.12) nor moderate (>30µmol/L; OR = 1.0, 95% CI = 0.54-1.81) hyperhomocysteinemia demonstrated significant correlations with ruptured aneurysms. Neither univariate (OR = 0.86; 95% CI 0.71-1.0) nor multivariable age-adjusted (OR = 0.91; 95% CI = 0.75-1.05) models evidenced an association between homocysteine levels and vasospasm. Homocysteinemia did not influence excellent functional outcomes at 6 months (mRS≤1) (OR = 1.04; 95% CI = 0.94-1.16). Conclusion There were no differences regarding homocysteinemia between patients with ruptured and unruptured intracranial aneurysms. In patients with ruptured aneurysms, homocysteinemia was not associated with vasospasm or functional outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Intracranial Aneurysmmentioning

confidence: 99%

Homocysteine serum levels in patients with ruptured and unruptured intracranial aneurysms: a case-control study

Mota Telles,

Rosi Junior,

Yamaki

et al. 2024

Arq Neuropsiquiatr

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“…In the development of cerebrovascular disease,DNA methylation may trigger lesions by altering the expression levels of genes related to vasoconstriction or vasoproliferation, which in turn affects changes in the levels of proteins related to vascular stability (He et al, 2022 ). DNA methylation is closely associated with the risk of IA (Nikkola et al, 2015 ; Zhou et al, 2017 ; Shafeeque et al, 2020 ; Wang et al, 2021 ). Kim et al’s study (Kim et al, 2022 ) showed that different genes with DNA methylation can be useful biomarkers for the accurate diagnosis of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.…”

Section: Discussionmentioning

confidence: 99%

“…DNA methylation is closely associated with the risk of IA (Nikkola et al, 2015;Zhou et al, 2017;Shafeeque et al, 2020;Wang et al, 2021). Kim et al's study (Kim et al, 2022) showed that different genes with DNA methylation can be useful biomarkers for the accurate diagnosis of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation of Patatin-Like Phospholipase Domain-Containing Protein 6 Gene Contributes to the Risk of Intracranial Aneurysm in Males

Zhou

Gong

et al. 2022

Front. Aging Neurosci.

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Objective: This study is aimed to investigate the contribution of patatin-like phospholipase domain-containing protein 6 (PNPLA6) DNA methylation to the risk of intracranial aneurysm (IA) in the Han Chinese population.Methods: A total of 96 age- and sex-matched participants were recruited to evaluate PNPLA6 methylation via bisulfite pyrosequencing. The PNPLA6 mRNA expression in the plasma was determined using real-time quantitative reverse transcription-polymerase chain reaction. Human primary artery smooth muscle cells (HPCASMC) were used for the in vitro function study.Results: PNPLA6 methylation was significantly higher in patients with IA than in healthy controls (p < 0.01). Sex group analysis showed that this correlation appeared in the male group (p < 0.01) but not in the female group (p > 0.05). PNPLA6 methylation was significantly associated with age in all participants (r = 0.306, p = 0.003) and in the control group (r = 0.377, p = 0.008) but not in the IA group (r = 0.127, p = 0.402). Furthermore, the PNPLA6 mRNA expression significantly decreased in patients with IA than that in the controls (p = 0.016). PNPLA6 expression was significantly inversely correlated with elevated DNA methylation in participants (r = −0.825, p < 0.0001). In addition, PNPLA6 transcription was significantly enhanced following treatment with 5-aza-2’-deoxycytidine methylation inhibitor in HPCASMC.The receiver operating characteristic analyses of curves showed that the PNPLA6 mean methylation [area under the curve (AUC) = 0.74, p < 0.001] and mRNA expression (AUC = 0.86, p < 0.001) could have a diagnostic value for patients with IA.Conclusion: Although future functional experiments are required to test our hypothesis, our study demonstrated that PNPLA6 methylation and mRNA expression were significantly associated with the risk of IA; thus, they show potential for use in the early diagnosis of IA.

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“…There are few IA biomarkers; these include plasma total homocysteine (tHcy), 6 which remains controversial. 7 8 tHcy is an amino acid generated by the metabolism of dietary methionine and is sensitive to vitamin B 12 , folate and various lifestyle factors.…”

Section: Introductionmentioning

confidence: 99%

A Mendelian randomisation, propensity score matching study to investigate causal association between serum homocysteine and intracranial aneurysm

et al. 2023

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Background and purposeRecent observational studies have reported that serum total homocysteine (tHcy) is associated with intracranial aneurysms (IAs). However, the causal effect of tHcy on IAs is unknown. We leveraged large-scale genetic association and real-world data to investigate the causal effect of tHcy on IA formation.MethodsWe performed a two-sample Mendelian randomisation (MR) using publicly available genome-wide association studies summary statistics to investigate the causal relationship between tHcy and IAs, following the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology-MR statement. Furthermore, a propensity score matching (PSM) analysis was conducted to evaluate the detailed effects of tHcy on risk of IA formation by utilizing real-world multicentre data, including 9902 patients with and without IAs (1:1 matched). Further interaction and subgroup analyses were performed to elucidate how tHcy affects risk of IA formation.ResultsMR analyses indicated that genetically determined tHcy was causally associated with IA risk (OR, 1.38, 95% CI 1.07 to 1.79; p=0.018). This is consistent with the more conservative weighted median analysis (OR, 1.41, 95% CI 1.03 to 1.93; p=0.039). Further sensitivity analyses showed no evidence of horizontal pleiotropy or heterogeneity of single nucleotide polymorphisms in causal inference. According to the PSM study, we found that, compared with low tHcy (≤15 µmol/L), moderate tHcy (>15–30 µmol/L) (OR 2.13, 95% CI 1.93 to 2.36) and high tHcy (>30 µmol/L) (OR 3.66, 95% CI 2.71 to 4.95) were associated with a higher IA risk (p trend <0.001). Subgroup analyses demonstrated significant ORs of tHcy in each subgroup when stratified by traditional cardiovascular risk factors. Furthermore, there was also a synergistic effect of tHcy and hypertension on IA risk (p interaction <0.001; the relative excess risk due to interaction=1.65, 95% CI 1.29 to 2.01).ConclusionBoth large-scale genetic evidence and multicentre real-world data support a causal association between tHcy and risk of IA formation. Serum tHcy may serve as a biomarker to identify high-risk individuals who would particularly benefit from folate supplementation.

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Methylation Map Genes Can be Critical in Determining the Methylome of Intracranial Aneurysm Patients

Cited by 4 publications

References 38 publications

Homocysteine serum levels in patients with ruptured and unruptured intracranial aneurysms: a case-control study

Homocysteine serum levels in patients with ruptured and unruptured intracranial aneurysms: a case-control study

DNA Methylation of Patatin-Like Phospholipase Domain-Containing Protein 6 Gene Contributes to the Risk of Intracranial Aneurysm in Males

A Mendelian randomisation, propensity score matching study to investigate causal association between serum homocysteine and intracranial aneurysm

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