Dataset Information

Combined Analysis of Interleukin-10 Gene Polymorphisms and Protein Expression in Children With Cerebral Palsy.

ABSTRACT: Background:Interleukin-10 (IL-10) is an important anti-inflammatory and immunosuppressive cytokine, and it has indispensable functions in both the onset and development of inflammatory disorders. The association between persistent inflammation and the development of cerebral palsy (CP) has attracted much attention. Objective:The purpose of this study was to investigate whether IL-10 gene polymorphisms and plasma protein expression are associated with CP and to analyze the role of IL-10 in CP. Methods:A total of 282 CP patients and 197 healthy controls were genotyped for IL-10 polymorphisms (rs1554286, rs1518111, rs3024490, rs1800871, and rs1800896). Among them, 95 CP patients and 93 healthy controls were selected for plasma IL-10 measurement. Results:The differences in the rs3024490 (p?=?0.033) and rs1800871 (p?=?0.033) allele frequencies of IL-10 were determined between CP patients and controls. The frequencies of allele and genotype between CP patients with spastic tetraplegia and normal controls of IL-10 polymorphisms showed significant differences for rs1554286, rs151811, rs3024490, rs1800871, and rs1800896 (pallele ?=?0.015, 0.009, 0.006, 0.003, and 0.006, pgenotype ?=?0.039, 0.018, 0.027, 0.012, and 0.03, respectively). The plasma IL-10 protein level in CP patients was higher than normal controls (9.13?±?0.77 vs. 6.73?±?0.63?pg/ml, p?=?0.017). IL-10 polymorphisms and protein association analysis showed that the TT genotype had higher plasma IL-10 protein levels compared to the GG?+?GT genotype at rs3024490 (11.14?±?7.27 vs. 7.44?±?6.95?pg/ml, p?=?0.045, respectively) in CP cases. Conclusion:These findings provide an important contribution toward explaining the pleiotropic role of IL-10 in the complex etiology of CP.

SUBMITTER: Xia L

PROVIDER: S-EPMC5874289 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Combined Analysis of <i>Interleukin-10</i> Gene Polymorphisms and Protein Expression in Children With Cerebral Palsy.

Xia Lei L Chen Mingjie M Bi Dan D Song Juan J Zhang Xiaoli X Wang Yangong Y Zhu Dengna D Shang Qing Q Xu Falin F Wang Xiaoyang X Xing Qinghe Q Zhu Changlian C

Frontiers in neurology 20180322

<h4>Background</h4>Interleukin-10 (IL-10) is an important anti-inflammatory and immunosuppressive cytokine, and it has indispensable functions in both the onset and development of inflammatory disorders. The association between persistent inflammation and the development of cerebral palsy (CP) has attracted much attention.<h4>Objective</h4>The purpose of this study was to investigate whether <i>IL-10</i> gene polymorphisms and plasma protein expression are associated with CP and to analyze the r ...[more]

PMID: 29623066

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Project description:Cerebral palsy (CP) is a group of non-progressive motor impairment syndromes that are secondary to brain injury in the early stages of brain development. Numerous etiologies and risk factors of CP have been reported, and genetic contributions have recently been identified. Autophagy has an important role in brain development and pathological process, and autophagy-related gene 7 (ATG7) is essential for autophagosome biogenesis. The purpose of this study was to investigate the genetic association between ATG7 gene single nucleotide polymorphisms (SNPs) and CP in Han Chinese children. Six SNPs (rs346078, rs1470612, rs11706903, rs2606750, rs2594972, and rs4684787) were genotyped in 715 CP patients and 658 healthy controls using the MassArray platform. Plasma ATG7 protein was determined in 73 CP patients and 79 healthy controls. The differences in the allele and genotype frequencies of the rs1470612 and rs2594972 SNPs were determined between the CP patients and controls (p allele = 0.02 and 0.0004, p genotype = 0.044 and 0.0012, respectively). Subgroup analysis revealed a more significant association of rs1470612 (p allele = 0.004, p genotype = 0.0036) and rs2594972 (p allele = 0.0004, p genotype < 0.0001) with male CP, and more significant differences in allele and genotype frequencies were also noticed between CP patients with spastic diplegia and controls for rs1470612 (p allele = 0.0024, p genotype = 0.008) and rs2594972 (p allele < 0.0001, p genotype = 0.006). The plasma ATG7 level was higher in CP patients compared to the controls (10.58 ± 0.85 vs. 8.18 ± 0.64 pg/mL, p = 0.024). The luciferase reporter gene assay showed that the T allele of rs2594972 SNP could significantly increase transcriptional activity of the ATG7 promoter compared to the C allele (p = 0.009). These findings suggest that an association exists between genetic variants of ATG7 and susceptibility to CP, which provides novel evidence for the role of ATG7 in CP and contributes to our understanding of the molecular mechanisms of this neurodevelopmental disorder.

Project description:Cerebral palsy is primarily an upper motor neuron disease that results in a spectrum of progressive movement disorders. Secondary to the neurological lesion, muscles from patients with cerebral palsy are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in cerebral palsy is a response to aberrant neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response to cerebral palsy using microarrays and correlating the transcriptional data with functional measures. Hamstring biopsies from gracilis and semitendinosus muscles were obtained from a cohort of patients with cerebral palsy (n=10) and typically developing patients (n=10) undergoing surgery. Affymetrix HG-U133A 2.0 chips (n=40) were used and expression data was verified for 6 transcripts using quantitative real-time PCR, as well as for two genes not on the microarray. Chips were clustered based on their expression and those from patients with cerebral palsy clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n=1,398). Significantly altered genes were analyzed for over-representation among gene ontologies, transcription factors, pathways, microRNA and muscle specific networks. These results centered on an increase in extracellular matrix expression in cerebral palsy as well as a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and novel therapies. Skeletal muscle biopsies from both the gracilis and semitendinosus were obtained during surgery for 20 pediatric subjects for affymetrix microarray analysis. We obtained a group of 10 patients undergoing medial hamstring lengthening in the cerebral palsy group and 10 patients undergoing ACL reconstruction with hamstring autograft in the control group. This provided 40 microarrays in 4 groups to analyze the effect of cerebral palsy and also differences between muscles.

Dataset Information

Combined Analysis of Interleukin-10 Gene Polymorphisms and Protein Expression in Children With Cerebral Palsy.

Publications

Combined Analysis of <i>Interleukin-10</i> Gene Polymorphisms and Protein Expression in Children With Cerebral Palsy.

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