Dataset Information

Association Between rs3833912/rs16944 SNPs and Risk for Cerebral Palsy in Mexican Children.

ABSTRACT: Perinatal asphyxia in the neonatal brain triggers a robust inflammatory response in which nitric oxide (NO) generation plays a hazardous role. Increased levels of NO can be maintained by the activity of inducible NO synthase (NOS2A) on its own or activated by IL-1beta (IL-1?) gene transcription and positive back stimulation of the NOS2 (CCTTT)n microsatellite by IL-1?, thus potentiating brain injury after ischemic perinatal asphyxia. We investigated whether the risk for cerebral palsy (CP) increases when an expansion of the -?2.5 kb (CCTTT)n microsatellite in the NOS2A gene and a single nucleotide polymorphism (SNP) in -C511T of the IL- IL-1? gene promoter occur in patients after perinatal hypoxic-ischemic encephalopathy. Genomic DNA was purified from peripheral leukocytes of 48 patients with CP and of 57 healthy control children. IL-1? SNP genotypes were established using a real-time PCR technique and fluorogenic probes and were validated by restriction fragment length polymorphism (RFLP) analysis using the AvaI restriction enzyme. The length of the CCTTTn microsatellite in the NOS2 gene promoter was determined by automated sequencing. The 14 repeat-long allele of the CCTTTn NOS2A microsatellite was present in 27% of CP patients vs 12.3% of controls, showing an odds ratio (OR)?=?2.6531 and 95% confidence interval (CI)?=?0.9612-7.3232 (P?

SUBMITTER: Torres-Merino S

PROVIDER: S-EPMC6394613 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Association Between rs3833912/rs16944 SNPs and Risk for Cerebral Palsy in Mexican Children.

Torres-Merino Sofia S Moreno-Sandoval Hayde Nallely HN Thompson-Bonilla Maria Del Rocio MDR Leon Josselyn Alejandra Orendain JAO Gomez-Conde Eduardo E Leon-Chavez Bertha Alicia BA Martinez-Fong Daniel D Gonzalez-Barrios Juan Antonio JA

Molecular neurobiology 20180621 3

Perinatal asphyxia in the neonatal brain triggers a robust inflammatory response in which nitric oxide (NO) generation plays a hazardous role. Increased levels of NO can be maintained by the activity of inducible NO synthase (NOS2A) on its own or activated by IL-1beta (IL-1β) gene transcription and positive back stimulation of the NOS2 (CCTTT)n microsatellite by IL-1β, thus potentiating brain injury after ischemic perinatal asphyxia. We investigated whether the risk for cerebral palsy (CP) incre ...[more]

PMID: 29931509

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Project description:IntroductionCerebral palsy (CP) is the most common motor disability in childhood, but its causes are only partly known. Early-life exposure to toxic metals and inadequate or excess amounts of essential elements can adversely affect brain and nervous system development. However, little is still known about these as perinatal risk factors for CP. This study aims to investigate the associations between second trimester maternal blood levels of toxic metals, essential elements, and mixtures thereof, with CP diagnoses in children.MethodsIn a large, population-based prospective birth cohort (The Norwegian Mother, Father, and Child Cohort Study), children with CP diagnoses were identified through The Norwegian Patient Registry and Cerebral Palsy Registry of Norway. One hundred forty-four children with CP and 1,082 controls were included. The relationship between maternal blood concentrations of five toxic metals and six essential elements and CP diagnoses were investigated using mixture approaches: elastic net with stability selection to identify important metals/elements in the mixture in relation to CP; then logistic regressions of the selected metals/elements to estimate odds ratio (OR) of CP and two-way interactions among metals/elements and with child sex and maternal education. Finally, the joint effects of the mixtures on CP diagnoses were estimated using quantile-based g-computation analyses.ResultsThe essential elements manganese and copper, as well as the toxic metal Hg, were the most important in relation to CP. Elevated maternal levels of copper (OR = 1.40) and manganese (OR = 1.20) were associated with increased risk of CP, while Hg levels were, counterintuitively, inversely related to CP. Metal/element interactions that were associated with CP were observed, and that sex and maternal education influenced the relationships between metals/elements and CP. In the joint mixture approach no significant association between the mixture of metals/elements and CP (OR = 1.00, 95% CI = [0.67, 1.50]) was identified.ConclusionUsing mixture approaches, elevated levels of copper and manganese measured in maternal blood during the second trimester could be related to increased risk of CP in children. The inverse associations between maternal Hg and CP could reflect Hg as a marker of maternal fish intake and thus nutrients beneficial for foetal brain development.

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

Association Between rs3833912/rs16944 SNPs and Risk for Cerebral Palsy in Mexican Children.

Publications

Association Between rs3833912/rs16944 SNPs and Risk for Cerebral Palsy in Mexican Children.

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