Polymorphism of TGF-β1 (rs1800469) in children with different degrees of myopia

Малачкова, Н. В.; Yatsenko, D. A.; Ljudkevich, G.; Shkarupa, V.N.

doi:10.31288/oftalmolzh201854548

Cited by 3 publications

(2 citation statements)

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“…It is well recognized that TGF‐β signalling directly affects ECM dynamics or triggers it when mediating other biological processes 38–41 . Herein, suppressed TGF‐β signalling in the zinc‐deficient conditions restrained ECM synthesis in HEK293.…”

Section: Discussionmentioning

confidence: 91%

SLC39A5 dysfunction impairs extracellular matrix synthesis in high myopia pathogenesis

Dong

Tian

Zhu

et al. 2021

J Cellular Molecular Medi

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High myopia is one of the leading causes of visual impairment worldwide with high heritability. We have previously identified the genetic contribution of SLC39A5 to nonsyndromic high myopia and demonstrated that disease‐related mutations of SLC39A5 dysregulate the TGF‐β pathway. In this study, the mechanisms underlying SLC39A5 involvement in the pathogenesis of high myopia are determined. We observed the morphogenesis and migration abnormalities of the SLC39A5 knockout (KO) human embryonic kidney cells (HEK293) and found a significant injury of ECM constituents. RNA‐seq and qRT‐PCR revealed the transcription decrease in COL1A1, COL2A1, COL4A1, FN1 and LAMA1 in the KO cells. Further, we demonstrated that TGF‐β signalling, the regulator of ECM, was inhibited in SLC39A5 depletion situation, wherein the activation of receptor Smads (R‐Smads) via phosphorylation was greatly blocked. SLC39A5 re‐expression reversed the phenotype of TGF‐β signalling and ECM synthesis in the KO cells. The fact that TGF‐β signalling was zinc‐regulated and that SLC39A5 was identified as a zinc transporter urged us to check the involvement of intracellular zinc in TGF‐β signalling impairment. Finally, we determined that insufficient zinc chelation destabilized Smad proteins, which naturally inhibited TGF‐β signalling. Overall, the SLC39A5 depletion–induced zinc deficiency destabilized Smad proteins, which inhibited the TGF‐β signalling and downstream ECM synthesis, thus contributing to the pathogenesis of high myopia. This discovery provides a deep insight into myopic development.

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Section: Discussionmentioning

confidence: 91%

SLC39A5 dysfunction impairs extracellular matrix synthesis in high myopia pathogenesis

Dong

Tian

Zhu

et al. 2021

J Cellular Molecular Medi

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“…In addition, the relative increase of serum TGF-β1 was significantly higher in carriers of the minor T allele as homozygous TT or heterozygous CT than in CTS patients with major C allele, indicating a possible functional role. Since TGF-β1 is a pleiotropic factor, previous studies have shown that decreased circulating TGF-β1 due to the rs1800469 CC genotype was associated with tumor progression and susceptibility [ 40 ], and myopia in the European population [ 41 ]. CTS patients carrying the TT genotype showed greatly increased serum MIP-1β levels than those with CT.…”

Section: Discussionmentioning

confidence: 99%

Serum Transforming Growth Factor β1 and Its Genetic Variants Are Associated with Increased Macrophage Inflammatory Protein 1β and Susceptibility to Idiopathic Carpal Tunnel Syndrome

Fattah

Selim²,

Fattah

et al. 2023

JPM

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Carpal tunnel syndrome (CTS) is a common entrapment neuropathy in which one of the body’s peripheral nerves becomes pinched or crushed. Transforming growth factor beta 1 (TGF-β1) plays an important role in the pathogenesis of CTS. An association between TGF-β1 polymorphisms and the susceptibility or progression of a number of diseases has been reported. In this study, three TGF-β1 single nucleotide polymorphisms (SNPs), serum TGF-β1, and macrophage inflammatory protein 1 beta (MIP-1β) were investigated as potential diagnostic markers for the progression of CTS in Egyptian patients. One hundred CTS patients and 100 healthy controls were recruited for the study. TGF-β1 SNPs +915G/C, −509C/T and −800G/A were determined by TaqMan genotyping assay. Serum TGF-β1 and MIP-1β levels were measured by ELISA. Serum TGF-β1 and MIP-1β levels increased significantly and were strongly correlated with the occurrence of CTS. The C allele of +915G/C, the T allele of −509C/T, and the G allele of −800G/A occurred more frequently in patients from CTS than in controls. The serum levels of TGF-β1 and MIP-1β in the group of carriers of the genotypes +915G/C GC and CC, the genotype −509C/T TT and the genotype −800G/A GA and AA were significantly higher in CTS patients. TGF-β1 and its +915G/C, −509C/T, and −800G/A SNPs and MIP-1β could be useful prognostic markers for the occurrence of CTS.

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Дослідження значення поліморфізму rs1107946 гена COL1A1 щодо розвитку міопії у дітей Подільського регіону України

Малачкова¹,

Yatsenko²,

Lyudkevich³

et al. 2021

AOU

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Дослідження значення поліморфізму rs1107946 гена COL1A1 щодо розвитку міопії у дітей Подільського регіону України Резюме. Серед механізмів патогенезу міопії важливе місце займають процеси, пов'язані з генетичними змінами структури і функції колагену. Колагенові волокна є найбільш численною складовою склери, на які припадає до 90 % сухої ваги фіброзної оболонки. При міопічному ремоделюванні склери експресія колагену, особливо колагену I типу, значно знижується. Частота алелей і розподіл генотипів за поліморфними варіантами rs1107946 гена COL1A1 серед досліджених дітей Подільського регіону України не відрізняються від середньоєвропейських значень цих показників. Частота варіантної алелі у дітей-міопів і дітей з еметропією становила 0,13 і 0,12 відповідно. Не виявлено вірогідної різниці в розподілі генотипів і частоті алельних варіантів rs1107946 гена COL1A1 між дослідженими групами. Для дітей Подільського регіону України поліморфізм rs1107946 гена COL1A1 не асоціюється з ризиком розвитку міопії.

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Polymorphism of TGF-β1 (rs1800469) in children with different degrees of myopia

Cited by 3 publications

References 0 publications

SLC39A5 dysfunction impairs extracellular matrix synthesis in high myopia pathogenesis

SLC39A5 dysfunction impairs extracellular matrix synthesis in high myopia pathogenesis

Serum Transforming Growth Factor β1 and Its Genetic Variants Are Associated with Increased Macrophage Inflammatory Protein 1β and Susceptibility to Idiopathic Carpal Tunnel Syndrome

Дослідження значення поліморфізму rs1107946 гена COL1A1 щодо розвитку міопії у дітей Подільського регіону України

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