Meta-analysis of Methylenetetrahydrofolate reductase maternal gene in Down syndrome: increased susceptibility in women carriers of the MTHFR 677T allele

Background: The presence of mitochondrial alterations in Down syndrome suggests that it might affect neuronal differentiation. We established a model of trisomic iPSCs, differentiating into neural precursor cells (NPCs) to monitor the occurrence of differentiation defects and mitochondrial dysfunction. Methods: Isogenic trisomic and euploid iPSCs were differentiated into NPCs in monolayer cultures using the dual-SMAD inhibition protocol. Expression of pluripotency and neural differentiation genes was assessed by qRT-PCR and immunofluorescence. Meta-analysis of expression data was performed on iPSCs. Mitochondrial Ca2+, reactive oxygen species (ROS) and ATP production were investigated using fluorescent probes. Oxygen consumption rate (OCR) was determined by Seahorse Analyzer. Results: NPCs at day 7 of induction uniformly expressed the differentiation markers PAX6, SOX2 and NESTIN but not the stemness marker OCT4. At day 21, trisomic NPCs expressed higher levels of typical glial differentiation genes. Expression profiles indicated that mitochondrial genes were dysregulated in trisomic iPSCs. Trisomic NPCs showed altered mitochondrial Ca2+, reduced OCR and ATP synthesis, and elevated ROS production. Conclusions: Human trisomic iPSCs can be rapidly and efficiently differentiated into NPC monolayers. The trisomic NPCs obtained exhibit greater glial-like differentiation potential than their euploid counterparts and manifest mitochondrial dysfunction as early as day 7 of neuronal differentiation.

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Correlation between Methylenetetrahydrofolate Reductase Polymorphisms and Hepatocellular Carcinoma: A Meta-Analysis

Annals of Nutrition and Metabolism ◽

10.1159/000496428 ◽

2019 ◽

Vol 74 (3) ◽

pp. 251-256 ◽

Cited By ~ 1

Author(s):

Hailong Su ◽

Guo Zhang

Keyword(s):

Hepatocellular Carcinoma ◽

Gene Polymorphisms ◽

Methylenetetrahydrofolate Reductase ◽

Meta Analysis ◽

Random Effect ◽

Recessive Model ◽

Mthfr Gene ◽

Systematic Research ◽

The Relationship ◽

Random Effect Models

Background: The correlation between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and hepatocellular carcinoma (HCC) remains controversial. Objectives: We performed this study to better assess the relationship between MTHFR gene polymorphisms and the likelihood of HCC. Methods: A systematic research of PubMed, Medline, and Embase was performed to retrieve relevant articles. ORs and 95% CIs were calculated. Results: A total of 15 studies with 8,378 participants were analyzed. In overall analyses, a significant association with the likelihood of HCC was detected for the rs1801131 polymorphism with fixed-effect models (FEMs) in recessive comparison (p = 0.002, OR 0.62, 95% CI 0.43–0.82). However, no positive results were detected for the rs1801133 polymorphism in any comparison. Further subgroup analyses revealed that the rs1801131 polymorphism was significantly associated with the likelihood of HCC in Asians with both FEMs (recessive model: p < 0.0001, OR 0.42, 95% CI 0.29–0.62; allele model: p = 0.004, OR 1.20, 95% CI 1.06–1.35) and random-effect models (recessive model: p = 0.002, OR 0.47, 95% CI 0.29–0.75). Nevertheless, we failed to detect any significant correlation between the rs1801133 polymorphism and HCC. Conclusions: Our findings indicated that the rs1801131 polymorphism may serve as a genetic biomarker of HCC in Asians.

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Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis

Tumor Biology ◽

10.1007/s13277-012-0395-2 ◽

2012 ◽

Vol 33 (5) ◽

pp. 1445-1454 ◽

Cited By ~ 47

Author(s):

Lin Yang ◽

Xin Hu ◽

Luhang Xu

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Methylenetetrahydrofolate Reductase ◽

Lymphoblastic Leukemia ◽

Meta Analysis ◽

Mthfr Polymorphisms

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Methylenetetrahydrofolate reductase gene C677T, A1298C polymorphisms and pre-eclampsia risk: a meta-analysis

Molecular Biology Reports ◽

10.1007/s11033-014-3415-z ◽

2014 ◽

Vol 41 (8) ◽

pp. 5435-5448 ◽

Cited By ~ 7

Author(s):

Xing Li ◽

Ya L. Luo ◽

Qiong H. Zhang ◽

Chen Mao ◽

Xi W. Wang ◽

...

Keyword(s):

Methylenetetrahydrofolate Reductase ◽

Meta Analysis ◽

Reductase Gene ◽

Methylenetetrahydrofolate Reductase Gene

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Tongue-Based Procedures in Treating Refractory Obstructive Sleep Apnea in Down Syndrome Patients: A Systematic Review and Meta-Analysis

FACE ◽

10.1177/2732501621992447 ◽

2021 ◽

Vol 2 (1) ◽

pp. 65-70

Author(s):

Paul B. Lee ◽

Michael T. Chung ◽

Jared Johnson ◽

Jordyn Lucas ◽

Caitlin R. Priest ◽

...

Keyword(s):

Systematic Review ◽

Obstructive Sleep Apnea ◽

Down Syndrome ◽

Sleep Apnea ◽

Nerve Stimulation ◽

Hypoglossal Nerve ◽

Meta Analysis ◽

Apnea Hypopnea Index ◽

Hypoglossal Nerve Stimulation ◽

Obstructive Sleep

Objective: There is a high prevalence of obstructive sleep apnea (OSA) in pediatric and adult Down Syndrome (DS) patients that is refractory to adenotonsillectomy and continuous positive airway pressure. Newer treatment modalities have emerged with improved outcomes. The objective is to provide an updated systematic review and meta-analysis to analyze the clinical outcomes of OSA in pediatric and adult DS patients with hypoglossal nerve stimulation using Inspire, midline posterior glossectomy plus lingual tonsillectomy (MPG + LT), and combined genioglossus advancement plus radiofrequency (GGS + RF). Methods: A comprehensive literature search of PubMed and Google Scholar was performed followed by a meta-analysis. Studies with preoperative and post-operative Apnea Hypopnea Index (AHI) values were included with patients serving as their own control. Results: Across 5 studies, 56 patients were analyzed. The mean reduction in AHI was statistically significant before vs. after procedure ( P < .001 for hypoglossal nerve stimulation using Inspire with a paired 2-tailed t-test and P = .031 for MPG + LT). Although individual patient AHI values were unavailable in the GGS + RF study, the standard difference in mean AHI was also significant for GGS + RF with P = .001. Device malfunction was the most common complication for Inspire while postoperative bleeding was observed for MPG + LT and nasopharyngeal obstruction and retropalatal collapse were observed for GGS + RF. Conclusion: This review reveals significant improvement in AHI with Inspire, MPG + LT, and GGS + RF for DS patients with refractory OSA. Further investigation is needed for comparison between these 3 therapies.

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