Leonardo C Ferreira, Josivan G Lima, Carolina O Mendes-Aguiar, Francisco P Freire-Neto, Paulo R P Nascimento, Glória R G Monteiro, Selma M B Jeronimo
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Study participants were also evaluated by densitometry (GE Lunar DPX), in addition to biochemical panel and pro-inflammatory cytokines measured in serum.</p><p><strong>Results: </strong>The gene expression profile of CGL1 was similar to CTRL, a result likely due to the compensatory activity of other AGPAT isoforms. CGL2 had 283 differentially expressed genes (DEGs), most enriched for neurodegenerative- and mitochondria-related genes. There was a negative correlation between the top1 gene, NUAK2, and fat mass (rho = -0.55, p = 0.01). The HET group had 105 DEGs, with OLR1, an atherogenic gene, as the most significant (P<sub>adj</sub> = 0.003). Up-regulation of TNF signaling pathway was also detected, a finding confirmed by high TNF and low IL10 levels in serum.</p><p><strong>Conclusion: </strong>Both CGL2 individuals and their unaffected relatives had abnormal gene expression pattern. 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引用次数: 0
摘要
背景：先天性全身性脂肪营养不良（CGL），又称Berardinelli-Seip综合征，是一种隐性遗传病。受影响的个体表现为肌肉骨骼异常、胰岛素抵抗、肝脂肪变性，并可能发展为心肌病和智力低下。AGPAT2 （CGL1）和BSCL2 （CGL2）突变与该综合征的联系机制尚不完全清楚。方法：在这里，我们分析了CGL1 （n = 3）、CGL2 （n = 12）、未受影响的BSCL2杂合子（HET, n = 8）和健康个体（CTRL, n = 3）的血细胞转录组。研究参与者还通过密度测定（GE Lunar DPX）、生化面板和血清促炎细胞因子进行评估。结果：CGL1的基因表达谱与CTRL相似，这可能与其他AGPAT亚型的代偿活性有关。CGL2有283个差异表达基因（DEGs），其中大多数为神经退行性和线粒体相关基因。top1基因、NUAK2与脂肪量呈负相关（rho = -0.55, p = 0.01）。HET组为105℃，其中致动脉粥样硬化基因OLR1最为显著（Padj = 0.003）。血清中高TNF和低il - 10水平证实了TNF信号通路的上调。结论：CGL2个体及其未患病亲属均存在基因表达异常。进一步的流行病学研究应寻求评估杂合子个体的心血管风险。
The blood transcriptome of the human congenital generalized lipodystrophy.
Background: Congenital generalized lipodystrophy (CGL), also known as Berardinelli-Seip syndrome, is a recessive genetic disease. Affected individuals present musculoskeletal abnormalities, insulin resistance, hepatic steatosis, and may develop cardiomyopathy and mental retardation The mechanism linking AGPAT2 (for CGL1) and BSCL2 (for CGL2) mutations to the syndrome has yet to be fully understood.
Methods: Here, we analyzed blood cell transcriptomes from individuals with CGL1 (n = 3), CGL2 (n = 12), unaffected BSCL2 heterozygotes (HET, n = 8), and healthy individuals (CTRL, n = 3). Study participants were also evaluated by densitometry (GE Lunar DPX), in addition to biochemical panel and pro-inflammatory cytokines measured in serum.
Results: The gene expression profile of CGL1 was similar to CTRL, a result likely due to the compensatory activity of other AGPAT isoforms. CGL2 had 283 differentially expressed genes (DEGs), most enriched for neurodegenerative- and mitochondria-related genes. There was a negative correlation between the top1 gene, NUAK2, and fat mass (rho = -0.55, p = 0.01). The HET group had 105 DEGs, with OLR1, an atherogenic gene, as the most significant (Padj = 0.003). Up-regulation of TNF signaling pathway was also detected, a finding confirmed by high TNF and low IL10 levels in serum.
Conclusion: Both CGL2 individuals and their unaffected relatives had abnormal gene expression pattern. Further epidemiological studies should seek to assess cardiovascular risk in heterozygote individuals.
期刊介绍：
Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology.
Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted.
Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.
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