@article{MTMT:35422606,
	title = {Severity Ranking of Missense and Frameshift Genetic Variants in SCD1 by In Silico and In Vitro Functional Analysis},
	url = {https://m2.mtmt.hu/api/publication/35422606},
	author = {Susán, Hanna and Orosz, Gabriella and Zámbó, Veronika and Csala, Miklós and Kereszturi, Éva},
	doi = {10.3390/nu16193259},
	journal-iso = {NUTRIENTS},
	journal = {NUTRIENTS},
	volume = {16},
	unique-id = {35422606},
	abstract = {Background: A considerable proportion of the symptoms associated with excessive dietary intake can be attributed to systemic imbalances in lipid metabolism. The prominent toxicity of saturated fatty acids has been repeatedly demonstrated and sheds light on the protective role of stearoyl-CoA desaturase-1 (SCD1), the key enzyme for fatty acid desaturation. SCD1 protein expression is regulated at the levels of transcription, translation, and degradation. However, the modulating effect of the variability of the human genome must also be taken into account. Therefore, we aimed to ascertain whether natural missense or frameshift mutations in SCD1 (p.H125P, p.M224L, p.A333T, p.R253AfsTer7) could influence the expression, degradation, or function of the enzyme. Methods: In silico and in vitro experiments were conducted to comprehensively evaluate the consequences associated with each genetic variation, with the objective of using the results to propose a risk or severity ranking of SCD1 variants. Results: As anticipated, the p.R253AfsTer7 variant was identified as the most deleterious in structural, functional, and quantitative terms. The p.H125P variant also reduced the desaturation capacity of the enzyme in accordance with the predicted structural alterations and augmented degradation resulting from folding complications. This was aggravated by increased mRNA instability and accompanied by mild endoplasmic reticulum stress induction. The p.A333T protein exhibited an intermediate phenotype, whereas p.M224L showed no deleterious effects and even increased the amount of SCD1. Conclusions: In conclusion, the large-scale identification of genetic variations needs to be supplemented with comprehensive functional characterization of these variations to facilitate adequate personalized prevention and treatment of lipid metabolism-related conditions.},
	year = {2024},
	eissn = {2072-6643},
	orcid-numbers = {Orosz, Gabriella/0000-0002-2030-287X; Csala, Miklós/0000-0002-3829-4361}
}

@article{MTMT:35166710,
	title = {Database-assisted screening of autism spectrum disorder related gene set},
	url = {https://m2.mtmt.hu/api/publication/35166710},
	author = {Kereszturi, Éva},
	doi = {10.1186/s13041-024-01127-0},
	journal-iso = {MOL BRAIN},
	journal = {MOLECULAR BRAIN},
	volume = {17},
	unique-id = {35166710},
	issn = {1756-6606},
	abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social and communication difficulties, along with repetitive behaviors. While genetic factors play a significant role in ASD, the precise genetic landscape remains complex and not fully understood, particularly in non-syndromic cases. The study performed an in silico comparison of three genetic databases. ClinVar, SFARI Gene, and AutDB were utilized to identify relevant gene subset and genetic variations associated with non-syndromic ASD. Gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) network analysis were conducted to elucidate the biological significance of the identified genes. The integrity of ASD-related gene subset and the distribution of their variations were statistically assessed. A subset of twenty overlapping genes potentially specific for non-syndromic ASD was identified. GSEA revealed enrichment of biological processes related to neuronal development and differentiation, synaptic function, and social skills, highlighting their importance in ASD pathogenesis. PPI network analysis demonstrated functional relationships among the identified genes. Analysis of genetic variations showed predominance of rare variants and database-specific distribution patterns. The results provide valuable insights into the genetic landscape of ASD and outline the genes and biological processes involved in the condition, while taking into account that the study relied exclusively on in silico analyses, which may be subject to biases inherent to database methodologies. Further research incorporating multi-omics data and experimental validation is warranted to enhance our understanding of non-syndromic ASD genetics and facilitate the development of targeted research, interventions and therapies.},
	year = {2024},
	eissn = {1756-6606}
}

@article{MTMT:34473748,
	title = {Allele-specific effect of various dietary fatty acids and ETS1 transcription factor on SCD1 expression},
	url = {https://m2.mtmt.hu/api/publication/34473748},
	author = {Tibori, Kinga and Zámbó, Veronika and Orosz, Gabriella and Szelényi, Péter and Sarnyai, Farkas and Tamási, Viola and Rónai, Zsolt and Csala, Miklós and Kereszturi, Éva},
	doi = {10.1038/s41598-023-50700-5},
	journal-iso = {SCI REP},
	journal = {SCIENTIFIC REPORTS},
	volume = {14},
	unique-id = {34473748},
	abstract = {Overnutrition and genetic predisposition are major risk factors for various metabolic disorders. Stearoyl-CoA desaturase-1 (SCD1) plays a key role in these conditions by synthesizing unsaturated fatty acids (FAs), thereby promoting fat storage and alleviating lipotoxicity. Expression of SCD1 is influenced by various saturated and cis-unsaturated FAs, but the possible role of dietary trans FAs (TFAs) and SCD1 promoter polymorphisms in its regulations has not been addressed. Therefore, we aimed to investigate the impact of the two main TFAs, vaccenate and elaidate, and four common promoter polymorphisms (rs1054411, rs670213, rs2275657, rs2275656) on SCD1 expression in HEK293T and HepG2 cell cultures using luciferase reporter assay, qPCR and immunoblotting. We found that SCD1 protein and mRNA levels as well as SCD1 promoter activity are markedly elevated by elaidate, but not altered by vaccenate. The promoter polymorphisms did not affect the basal transcriptional activity of SCD1 . However, the minor allele of rs1054411 increased SCD1 expression in the presence of various FAs. Moreover, this variant was predicted in silico and verified in vitro to reduce the binding of ETS1 transcription factor to SCD1 promoter. Although we could not confirm an association with type 2 diabetes mellitus, the FA-dependent and ETS1-mediated effect of rs1054411 polymorphism deserves further investigation as it may modulate the development of lipid metabolism-related conditions.},
	year = {2024},
	eissn = {2045-2322},
	orcid-numbers = {Tibori, Kinga/0000-0002-6808-4015; Orosz, Gabriella/0000-0002-2030-287X; Sarnyai, Farkas/0000-0002-5525-5508; Tamási, Viola/0000-0001-7419-5603; Rónai, Zsolt/0000-0002-0909-7932; Csala, Miklós/0000-0002-3829-4361}
}

@article{MTMT:34430014,
	title = {Diversity and Classification of Genetic Variations in Autism Spectrum Disorder},
	url = {https://m2.mtmt.hu/api/publication/34430014},
	author = {Kereszturi, Éva},
	doi = {10.3390/ijms242316768},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {34430014},
	issn = {1661-6596},
	abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental condition with symptoms that affect the whole personality and all aspects of life. Although there is a high degree of heterogeneity in both its etiology and its characteristic behavioral patterns, the disorder is well-captured along the autistic triad. Currently, ASD status can be confirmed following an assessment of behavioral features, but there is a growing emphasis on conceptualizing autism as a spectrum, which allows for establishing a diagnosis based on the level of support need, free of discrete categories. Since ASD has a high genetic predominance, the number of genetic variations identified in the background of the condition is increasing exponentially as genetic testing methods are rapidly evolving. However, due to the huge amount of data to be analyzed, grouping the different DNA variations is still challenging. Therefore, in the present review, a multidimensional classification scheme was developed to accommodate most of the currently known genetic variants associated with autism. Genetic variations have been grouped according to six criteria (extent, time of onset, information content, frequency, number of genes involved, inheritance pattern), which are themselves not discrete categories, but form a coherent continuum in line with the autism spectrum approach.},
	year = {2023},
	eissn = {1422-0067}
}

@article{MTMT:33726492,
	title = {High fat diet and PCSK9 knockout modulates lipid profile of the liver and changes the expression of lipid homeostasis related genes},
	url = {https://m2.mtmt.hu/api/publication/33726492},
	author = {Németh, Krisztina and Tóth, Blanka and Sarnyai, Farkas and Koncz, Anna and Lenzinger, Dorina and Kereszturi, Éva and Visnovitz, Tamás and Kestecher, Brachyahu Meir and Osteikoetxea, Xabier and Csala, Miklós and Buzás, Edit Irén and Tamási, Viola},
	doi = {10.1186/s12986-023-00738-z},
	journal-iso = {NUTR METAB},
	journal = {NUTRITION & METABOLISM},
	volume = {20},
	unique-id = {33726492},
	issn = {1743-7075},
	year = {2023},
	eissn = {1743-7075},
	orcid-numbers = {Németh, Krisztina/0000-0002-3825-2137; Sarnyai, Farkas/0000-0002-5525-5508; Koncz, Anna/0000-0003-2511-2394; Visnovitz, Tamás/0000-0002-7962-5083; Osteikoetxea, Xabier/0000-0003-3628-0174; Csala, Miklós/0000-0002-3829-4361; Buzás, Edit Irén/0000-0002-3744-206X; Tamási, Viola/0000-0001-7419-5603}
}

@article{MTMT:33726454,
	title = {Molecular Basis of Unequal Alternative Splicing of Human SCD5 and Its Alteration by Natural Genetic Variations},
	url = {https://m2.mtmt.hu/api/publication/33726454},
	author = {Orosz, Gabriella and Szabó, Luca and Bereti, Szanna and Zámbó, Veronika and Csala, Miklós and Kereszturi, Éva},
	doi = {10.3390/ijms24076517},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {33726454},
	issn = {1661-6596},
	abstract = {Alternative splicing (AS) is a major means of post-transcriptional control of gene expression, and provides a dynamic versatility of protein isoforms. Cancer-related AS disorders have diagnostic, prognostic and therapeutic values. Changes in the expression and AS of human stearoyl-CoA desaturase-5 (SCD5) are promising specific tumor markers, although the transcript variants (TVs) of the gene have not yet been confirmed. Our in silico, in vitro and in vivo study focuses on the distribution of SCD5 TVs (A and B) in human tissues, the functionality of the relevant splice sites, and their modulation by certain single-nucleotide variations (SNVs). An order of magnitude higher SCD5A expression was found compared with SCD5B. This unequal splicing is attributed to a weaker recognition of the SCD5B-specific splicing acceptor site, based on predictions confirmed by an optimized minigene assay. The pronounced dominance of SCD5A was largely modified (rs1430176385_A, rs1011850309_A) or even inverted (rs1011850309_C) by natural SNVs at the TV-specific splice sites. Our results provide long missing data on the proportion of SCD5 TVs in human tissues and reveal mutation-driven changes in SCD5 AS, potentially affecting tumor-associated reprogramming of lipid metabolism, thus having prognostic significance, which may be utilized for novel and personalized therapeutic approaches.},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Orosz, Gabriella/0000-0002-2030-287X; Szabó, Luca/0000-0002-1907-9957; Csala, Miklós/0000-0002-3829-4361}
}

@article{MTMT:33132846,
	title = {A Single Nucleotide Polymorphism (rs3811792) Affecting Human SCD5 Promoter Activity Is Associated with Diabetes Mellitus},
	url = {https://m2.mtmt.hu/api/publication/33132846},
	author = {Zámbó, Veronika and Orosz, Gabriella and Szabó, Luca and Tibori, Kinga and Sipeki, Szabolcs and Molnár, Krisztina and Csala, Miklós and Kereszturi, Éva},
	doi = {10.3390/genes13101784},
	journal-iso = {GENES-BASEL},
	journal = {GENES},
	volume = {13},
	unique-id = {33132846},
	issn = {2073-4425},
	abstract = {The combined prevalence of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus is 10.5% worldwide and this is constantly increasing. The pathophysiology of the diseases include disturbances of the lipid metabolism, in which acyl-CoA desaturases play a central role as they synthesize unsaturated fatty acids, thereby providing protection against lipotoxicity. The stearoyl-CoA desaturase-5 (SCD5) isoform has received little scientific attention. We aimed to investigate the SCD5 promoter and its polymorphisms in vitro, in silico and in a case-control study. The SCD5 promoter region was determined by a luciferase reporter system in HepG2, HEK293T and SK-N-FI cells and it was proved to be cell type-specific, but it was insensitive to different fatty acids. The effect of the SCD5 promoter polymorphisms rs6841081 and rs3811792 was tested in the transfected cells. The T allele of rs3811792 single nucleotide polymorphism (SNP) significantly reduced the activity of the SCD5 promoter in vitro and modified several transcription factor binding sites in silico. A statistically significant association of rs3811792 SNP with T1DM and T2DM was also found, thus supporting the medical relevance of this variation and the complexity of the molecular mechanisms in the development of metabolic disorders. In conclusion, the minor allele of rs3811792 polymorphism might contribute to the development of diabetes by influencing the SCD5 promoter activity.},
	year = {2022},
	eissn = {2073-4425},
	orcid-numbers = {Orosz, Gabriella/0000-0002-2030-287X; Szabó, Luca/0000-0002-1907-9957; Tibori, Kinga/0000-0002-6808-4015; Sipeki, Szabolcs/0000-0002-9678-6743; Molnár, Krisztina/0009-0004-4754-0423; Csala, Miklós/0000-0002-3829-4361}
}

@article{MTMT:32915695,
	title = {Different Metabolism and Toxicity of TRANS Fatty Acids, Elaidate and Vaccenate Compared to Cis-Oleate in Hepg2 Cells},
	url = {https://m2.mtmt.hu/api/publication/32915695},
	author = {Sarnyai, Farkas and Kereszturi, Éva and Szirmai, Kitti and Mátyási, Judit and Al-Hag, Johanna Iman and Csizmadia, Tamás and Lőw, Péter and Szelényi, Péter and Tamási, Viola and Tibori, Kinga and Zámbó, Veronika and Tóth, Blanka and Csala, Miklós},
	doi = {10.3390/ijms23137298},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {23},
	unique-id = {32915695},
	issn = {1661-6596},
	year = {2022},
	eissn = {1422-0067},
	orcid-numbers = {Sarnyai, Farkas/0000-0002-5525-5508; Csizmadia, Tamás/0000-0002-2098-9165; Lőw, Péter/0000-0003-2450-7087; Tamási, Viola/0000-0001-7419-5603; Tibori, Kinga/0000-0002-6808-4015; Csala, Miklós/0000-0002-3829-4361}
}

@article{MTMT:32860601,
	title = {Molecular Mechanisms Underlying the Elevated Expression of a Potentially Type 2 Diabetes Mellitus Associated SCD1 Variant},
	url = {https://m2.mtmt.hu/api/publication/32860601},
	author = {Tibori, Kinga and Orosz, Gabriella and Zámbó, Veronika and Szelényi, Péter and Sarnyai, Farkas and Tamási, Viola and Rónai, Zsolt and Mátyási, Judit and Tóth, Blanka and Csala, Miklós and Kereszturi, Éva},
	doi = {10.3390/ijms23116221},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {23},
	unique-id = {32860601},
	issn = {1661-6596},
	year = {2022},
	eissn = {1422-0067},
	orcid-numbers = {Tibori, Kinga/0000-0002-6808-4015; Orosz, Gabriella/0000-0002-2030-287X; Sarnyai, Farkas/0000-0002-5525-5508; Tamási, Viola/0000-0001-7419-5603; Rónai, Zsolt/0000-0002-0909-7932; Csala, Miklós/0000-0002-3829-4361}
}

@article{MTMT:31276673,
	title = {Effect of cis- and trans-Monounsaturated Fatty Acids on Palmitate Toxicity and on Palmitate-induced Accumulation of Ceramides and Diglycerides},
	url = {https://m2.mtmt.hu/api/publication/31276673},
	author = {Sarnyai, Farkas and Somogyi, Anna and Gór-Nagy, Zsófia and Zámbó, Veronika and Szelényi, Péter and Mátyási, Judit and Simon-Szabó, Laura and Kereszturi, Éva and Tóth, Blanka and Csala, Miklós},
	doi = {10.3390/ijms21072626},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {21},
	unique-id = {31276673},
	issn = {1661-6596},
	year = {2020},
	eissn = {1422-0067},
	orcid-numbers = {Sarnyai, Farkas/0000-0002-5525-5508; Somogyi, Anna/0000-0002-8656-336X; Csala, Miklós/0000-0002-3829-4361}
}