Malonylcarnitine in Newborns with Non‐syndromic Cleft Lip with or without Cleft Palate

Hozyasz, Kamil K.; Oltarzewski, Mariusz; Dudkiewicz, Zofia

doi:10.4248/ijos10047

Cited by 9 publications

(5 citation statements)

References 34 publications

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“…Malonylcarnitine (C3DC) was suggested to be an indicator to reflect malonyl-CoA levels (40). Malonyl-CoA is one of the key regulators in mammalian energy homeostasis by inhibiting mitochondrial CPT1 and FAO (41).…”

Section: Discussionmentioning

confidence: 99%

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

et al. 2016

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OBJECTIVEAcylcarnitines were suggested as early biomarkers even prior to insulin resistance in animal studies, but their roles in predicting type 2 diabetes were unknown. Therefore, we aimed to determine whether acylcarnitines could independently predict type 2 diabetes by using a targeted metabolic profiling approach. RESEARCH DESIGN AND METHODSA population-based prospective study was conducted among 2,103 communityliving Chinese individuals aged 50-70 years from Beijing and Shanghai with a mean follow-up duration of 6 years. Fasting glucose, glycohemoglobin, and insulin were determined at baseline and in a follow-up survey. Baseline plasma acylcarnitines were profiled by liquid chromatography-tandem mass spectrometry. RESULTSOver the 6-year period, 507 participants developed diabetes. A panel of acylcanitines, especially with long chain, was significantly associated with increased risk of type 2 diabetes. The relative risks of type 2 diabetes per SD increase of the predictive model score were 2.48 (95% CI 2.20-2.78) for the conventional and 9.41 (95% CI 7.62-11.62) for the full model including acylcarnitines, respectively. Moreover, adding selected acylcarnitines substantially improved predictive ability for incident diabetes, as area under the receiver operator characteristic curve improved to 0.89 in the full model compared with 0.73 in the conventional model. Similar associations were obtained when the predictive models were established separately among Beijing or Shanghai residents. CONCLUSIONSA panel of acylcarnitines, mainly involving mitochondrial lipid dysregulation, significantly improved predictive ability for type 2 diabetes beyond conventional risk factors. These findings need to be replicated in other populations, and the underlying mechanisms should be elucidated.The escalating global epidemic of type 2 diabetes has contributed considerably to socioeconomic burdens in both developed and developing countries (1). To understand biological mechanisms and improve clinical predictions, it is essential to identify novel biomarkers to enhance the capability to predict early pathophysiological changes (2). As a largely preventable disease, early prediction is the key to control the epidemic trend of type 2 diabetes, particularly in those countries with

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Section: Discussionmentioning

confidence: 99%

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

et al. 2016

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“…Cleft palate can be caused by mutations in a variety of genes including transcription factors, growth factor receptors, extracellular matrix components, and cell surface adhesion molecules and decreased malonylcarnitine . Thyroid transcription factor‐2 was first identified as a thyroid‐specific DNA binding factor recognizing thyroglobulin (Tg) and thyroperoxidase (TPO) promoters.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of mouse TTF‐2 gene causes cleft palate

Meng

Shi

et al. 2012

J Cellular Molecular Medi

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In humans, mutations of the gene encoding for thyroid transcription factor-2 (TTF-2 or FOXE1) result in Bamforth syndrome. Bamforth syndrome is characterized by agenesis, cleft palate, spiky hair and choanal atresia. TTF-2 null mice (TTF-2−/−) also exhibit cleft palate, suggesting its involvement in the palatogenesis. However, the molecular pathology and genetic regulation by TTF2 remain largely unknown. In the present study, the recombinant expression vector pBROAD3-TTF-2 containing the promoter of the mouse ROSA26 gene was created to form the structural gene of mouse TTF-2 and was microinjected into the male pronuclei of fertilized ova. Sequence analysis confirmed that the TTF-2 transgenic mouse model was established successfully. The transgenic mice displayed a phenotype of cleft palate. In addition, we found that TTF-2 was highly expressed in the medial edge epithelium (MEE) from the embryonic day 12.5 (E12.5) to E14.5 in TTF-2 transgenic mice. These observations suggest that overexpression of TTF-2 during palatogenesis may contribute to formation of cleft palate.

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“…Patients with congenital deficiency of this enzyme presented elevated C3DC levels 66 ; therefore, C3DC may be reflective of malonyl-CoA level. 67 Higher serum C3DC level was also reported in cases of diabetes mellitus 68,69 and chronic kidney disease. 70 Nevertheless, angiogenesis wise, fatty acid oxidation is critical for ECs in that CPT1A knockdown diminishes angiogenesis.…”

Section: C3dcmentioning

confidence: 89%

Targeted Blood Metabolomic Study on Retinopathy of Prematurity

Yang

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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This study aims at exploring alterations of major metabolites and metabolic pathways in retinopathy of prematurity (ROP) infants and identifying biomarkers that may merit early diagnosis of ROP. METHODS. We analyzed targeted metabolites from 81 premature infants (<34 weeks of gestational age), including 40 ROP cases (15 males and 25 females, birth weight 1.263 ± 0. 345 kg, gestational age 31.20 ± 4.62 weeks) and 41 cases (30 males, 11 females, birth weight 1.220 ± 0.293 kg, gestational age 30.96 ± 4.17 weeks) of well-matched non-ROP controls. Metabolites were measured by ultra-performance liquid chromatographytandem mass spectrometry. Standard multivariate and univariate analysis was performed to interpret metabolomic results. RESULTS. Glycine, glutamate, leucine, serine, piperidine, valine, tryptophan, citrulline, malonyl carnitine (C3DC), and homocysteine were identified as the top discriminant metabolites. In particular, discriminant concentrations of C3DC and glycine were also confirmed by univariate analysis as statistically significant different between ROP and non-ROP infants. CONCLUSIONS. This study gained an insight into the metabolomic aspects of ROP development. We suggest that higher blood levels of C3DC and glycine can be promising biomarkers to predict the occurrence, but not the severity of ROP.

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Malonylcarnitine in Newborns with Non‐syndromic Cleft Lip with or without Cleft Palate

Cited by 9 publications

References 34 publications

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study

Overexpression of mouse TTF‐2 gene causes cleft palate

Targeted Blood Metabolomic Study on Retinopathy of Prematurity

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