6 research outputs found
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Evaluation of SPARC as a candidate gene of juvenile-onset primary open-angle glaucoma by mutation and copy number analyses
Purpose: To investigate the involvement of SPARC (secreted protein acidic and rich in cysteine) mutations and copy number variation in juvenile-onset primary open-angle glaucoma (JPOAG). Methods: This study involved the 27 family members from the GLC1M (glaucoma 1, open angle, M)-linked Philippine pedigree with JPOAG, 46 unrelated Chinese patients with JPOAG and 95 controls. Mutation screening of the SPARC sequence, covering the promoter, 5′-untranslated region (UTR), entire coding regions, exon-intron boundaries, and part of the 3′-UTR, was performed using polymerase chain reaction and direct DNA sequencing. Copy number of the gene was analyzed by three TaqMan copy number assays. Results: No putative SPARC mutation was detected in the Philippine family. In the Chinese participants, 11 sequence variants were detected. Two were novel: IVS2+8G>T and IVS2+32C>T. For the 9 known SNPs, one was synonymous (rs2304052, p.Glu22Glu) and the others were located in noncoding regions. No individual SNP was associated with JPOAG. Five of the most common SNPs, i.e., rs2116780, rs1978707, rs7719521, rs729853, and rs1053411, were contained in a LD (linkage disequilibrium) block. Haplotype-based analysis showed that no haplotype was associated with the disorder. Copy number analysis revealed that all study subjects had two copies of the gene, suggesting no correlation between the copy number of SPARC and JPOAG. Conclusions: We have excluded SPARC as the causal gene at the GLC1M locus in the Philippine pedigree and, for the first time, revealed that the coding sequences, splice sites and copy number of SPARC do not contribute to JPOAG. Further investigations are warranted to unravel the involvement of SPARC in the pathogenesis of other forms of glaucoma
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SNP rs1533428 at 2p16.3 as a marker for late-onset primary open-angle glaucoma
Purpose: To investigate the associations between gene variants in cholesterol 24S-hydroxylase (CYP46A1), LIM homeobox transcription factor 1-beta (LMX1B), plexin domain containing 2 (PLXDC2), toll-like receptor 4 (TLR4), transmembrane and tetratricopeptide repeat containing 2 (TMTC2), zona pellucida glycoprotein 4 (ZP4), chromosome 2p16.3, and primary open-angle glaucoma (POAG). Methods: We studied 462 POAG patients and 577 controls from three cohorts (Hong Kong, Shantou, and Beijing, China). Twelve single-nucleotide polymorphisms (SNPs) were genotyped in the Hong Kong cohort using TaqMan genotyping assay. Significant associations were validated in the Shantou and Beijing cohorts. Results: Association of POAG with TLR4 rs7037117, in a recessive model, was identified in the Hong Kong and Shantou cohorts (both southern Chinese, =0.0019) but not the Beijing cohort (northern Chinese). rs1533428 at chromosome 2p16.3 showed a consistent trend of age-specific association in all three cohorts. Genotypes TT + CT conferred a 2.16 fold of significantly increased risk to late-onset POAG (=0.00025), but no significant risk to POAG of younger ages of onset in the combined cohort. A joint effect was found between rs7037117 and rs1533428, with carriers of both higher-risk genotypes having a 4.53 fold of increased disease risk (p=0.00028). Conclusions: Our study reveals discrepant association patterns of 12 candidate SNPs in 7 genes/loci with POAG in Chinese, provides positive replications for POAG markers rs1533428 at 2p16.3 and TLR4 rs7037117, and suggests that rs1533428 is a putative risk variant for late-onset POAG. The identification of an age-specific association between rs1533428 and late-onset POAG highlights a new genotype-phenotype association in POAG. Further studies are warranted to confirm the age-specific association
The efficacy of physical exercise interventions on mental health, cognitive function, and ADHD symptoms in children and adolescents with ADHD: an umbrella reviewResearch in context
Summary: Background: A considerable number of published reviews have addressed the effects of physical exercise on mental health, cognitive function, or attention-deficit hyperactivity (ADHD) symptoms as outcomes in children and adolescents with ADHD. Their findings have often conflicted, therefore, there is an urgent need to synthesise a hierarchy of the evidence and examine the credibility of previous meta-analyses. To establish the robustness of these findings, we conducted an additional meta-analysis on a number of individual studies that were not covered in previous reviews but were suitable for inclusion in our own study. Methods: Three reviewers independently searched Web of Science, Psych INFO, Embase, Cochrane Library, PubMed, SPORTDiscus, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) for meta-analyses published between database inceptions to December 1, 2022. The individual studies were also screened from 1 January 2015 to 1 December 2022. We included meta-analyses and eligible individual studies that addressed the effects of exercise on at least one outcome of mental health, cognitive function, or ADHD symptoms in children and adolescents with ADHD. We excluded systematic reviews and articles that lacked sufficient data for a meaningful second analysis. The effect estimates (Hedges’ g), 95% confidence interval (95% CI), 95% prediction interval (95% PI), small study effects, and excess significance bias were calculated. Finally, we categorised the meta-analyses based on the credibility of the evidence criteria and their quality using a Measurement Tool to Assess Systematic Reviews 2 checklist. This umbrella review was registered with PROSPERO, CRD42022361331. Findings: Of 181 listed review articles and 60 individual papers, 10 reviews and 12 individual articles were included in the meta-analyses. This yielded 37 meta-analyses based on 106 study estimates. Evidence was highly suggestive for the effectiveness of exercise (class II) for improving inattention (G = 0.92, 95% CI: 0.44–1.39, 95%), inhibitory control (G = 0.82, 95% CI: 0.52–1.13), and cognitive flexibility (G = 0.52, 95% CI: 0.32–0.72). However, evidence for the effectiveness of exercise on emotional, social, and working memory outcomes was weak, and these results were not significant for hyperactivity and behavioural functioning. Interpretation: Improvement of cognitive flexibility, inhibitory control, and inattention in children and adolescents with ADHD was highly suggested by exercise interventions. However, results were weak for other outcomes (emotional functioning, social functioning, and working memory). Further high-quality randomised controlled trials are, therefore, warranted to determine the effectiveness of exercise on weak outcomes. Funding: None