Comparison of blood pressure levels among four age groups of Chinese children matched by height

Hypertension in children is frequently undiagnosed. Normal blood pressure is currently defined as a function of two continuous variables, age and height for each gender. Applying the current cutoff values to assess a child's blood pressure is time consuming. To separate the independent effect of age from that of height on blood pressure, we conducted a multiple group matched study to investigate if blood pressure levels in children with a given height distribution vary with age. An equal number of 2539 Chinese children from each of the four age groups (7, 8, 9 and 10 years) were individually matched by height, sex and geographic region. We used the matching technique to force the four age groups to have an identical height distribution. Systolic and diastolic blood pressures significantly increased with increasing age before matching. After matching, four groups had strikingly similar levels of blood pressures, and the differences among four groups were small and not statistically significant. Once height is taken into consideration, age has little impact on blood pressure. Our findings, if confirmed in children of other ages, suggest that blood pressure percentile charts can be considerably simplified by establishing normal percentiles according to height alone for each gender

Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations.

Background Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC. Methods Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis. Results Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages. Conclusions The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies

Meteorologically estimated exposure but not distance predicts asthma symptoms in schoolchildren in the environs of a petrochemical refinery: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Community concern about asthma prompted an epidemiological study of children living near a petrochemical refinery in Cape Town, South Africa. Because of resource constraints and the complexity of refinery emissions, neither direct environmental measurements nor modelling of airborne pollutants was possible. Instead a meteorologically derived exposure metric was calculated with the refinery as the putative point source. The study aimed to determine whether (1) asthma symptom prevalences were elevated compared to comparable areas in Cape Town and (2) whether there was an association between asthma symptom prevalences and the derived exposure metric.</p> <p>Methods</p> <p>A cross-sectional study was carried out of all consenting school children aged 11 to 14 years attending schools in a defined area, utilizing the International Study of Asthma and Allergy in Childhood (ISAAC) written and video questionnaires. Information was collected on potential confounders, e.g. parental history of atopic disease, active and passive smoking by the participant, birth order, number of children in the home and distance from a major road. The exposure metric combined residential distance of each child from the refinery with a wind vector in the form of wind speed, wind direction and proportion of the year blown.</p> <p>Results</p> <p>A total of 2,361 children from 17 schools met the criteria for inclusion. In multivariate analysis, meteorologically estimated exposure (MEE), but not simple distance from the refinery, was positively associated with having to take an inhaler to school [odds ratio per interquartile range (OR) 1.22, 95% confidence interval (CI) 1.06-1.40], and with a number of video elicited asthma symptoms, including recent waking with wheezing (OR 1.33, 95% CI 1.06-1.66) and frequent wheezing at rest (OR 1.27, 95% CI 1.05 - 1.54). Symptom prevalences were higher than in other areas of the city, with frequent waking with wheezing being in great excess (OR 8.92, 95% CI 4.79-16.63).</p> <p>Conclusion</p> <p>The results support the hypothesis of an increased prevalence of asthma symptoms among children in the area as a result of refinery emissions and provide a substantive basis for community concern. The methodology also provides a low cost means of testing hypotheses about point source pollutant effects on surrounding populations of children.</p

Low copy numbers of complement C4 and C4A deficiency are risk factors for myositis, its subgroups and autoantibodies

Background Idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterised by myositis-related autoantibodies plus infiltration of leucocytes into muscles and/or the skin, leading to the destruction of blood vessels and muscle fibres, chronic weakness and fatigue. While complement-mediated destruction of capillary endothelia is implicated in paediatric and adult dermatomyositis, the complex diversity of complement C4 in IIM pathology was unknown. Methods We elucidated the gene copy number (GCN) variations of total C4, C4A and C4B, long and short genes in 1644 Caucasian patients with IIM, plus 3526 matched healthy controls using real-time PCR or Southern blot analyses. Plasma complement levels were determined by single radial immunodiffusion. Results The large study populations helped establish the distribution patterns of various C4 GCN groups. Low GCNs of C4T (C4T=2+3) and C4A deficiency (C4A=0+1) were strongly correlated with increased risk of IIM with OR equalled to 2.58 (2.28-2.91), p=5.0×10 -53 for C4T, and 2.82 (2.48-3.21), p=7.0×10 -57 for C4A deficiency. Contingency and regression analyses showed that among patients with C4A deficiency, the presence of HLA-DR3 became insignificant as a risk factor in IIM except for inclusion body myositis (IBM), by which 98.2% had HLA-DR3 with an OR of 11.02 (1.44-84.4). Intragroup analyses of patients with IIM for C4 protein levels and IIM-related autoantibodies showed that those with anti-Jo-1 or with anti-PM/Scl had significantly lower C4 plasma concentrations than those without these autoantibodies. Conclusions C4A deficiency is relevant in dermatomyositis, HLA-DRB1∗03 is important in IBM and both C4A deficiency and HLA-DRB1∗03 contribute interactively to risk of polymyositis