1,721,596 research outputs found
Statins as modulators of bone formation
No full textThe use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) to reduce serum cholesterol is well described. However, the recent finding that statins have direct effects on bone was unexpected. A number of epidemiological studies have recently been published that explore the effects of statins on bone mineral density and risk of fracture in humans. Statins may act by directly stimulating the expression of bone morphogenetic protein-2 and increasing osteoblast differentiation or, like nitrogen-containing bisphosphonates, may have effects on the mevalonate pathway that leads to inhibition of osteoclast activity and osteoblast apoptosis. In addition, the demonstration that statins can inhibit inflammation and encourage angiogenesis offers other possibilities for action
Twin studies advance the understanding of gene-environment interplay in human nutrigenomics
Get PDFInvestigations into the genetic architecture of diet-disease relationships are particularly relevant today with the global epidemic of obesity and chronic disease. Twin studies have demonstrated that genetic makeup plays a significant role in a multitude of dietary phenotypes such as energy and macronutrient intakes, dietary patterns, and specific food group intakes. Besides estimating heritability of dietary assessment, twins provide a naturally unique, case-control experiment. Due to their shared upbringing, matched genes and sex (in the case of monozygotic (MZ) twin pairs), and age, twins provide many advantages over classic epidemiological approaches. Future genetic epidemiological studies could benefit from the twin approach particularly where defining what is 'normal' is problematic due to the high inter-individual variability underlying metabolism. Here, we discuss the use of twins to generate heritability estimates of food intake phenotypes. We then highlight the value of discordant MZ pairs to further nutrition research through discovery and validation of biomarkers of intake and health status in collaboration with cutting-edge omics technologies.</p
Blood, urine and faecal metabolite profiles in the study of adult renal disease
No full textChronic kidney disease (CKD) is a major public health burden and to date traditional biomarkers of renal function (such as serum creatinine and cystatin C) are unable to identify at-risk individuals before the disease process is well under way. To help preventive strategies and maximize the potential for effective interventions, it is important to characterise the molecular changes that take place in the development of renal damage. Metabolomics is a promising tool to identify markers of renal disease since the kidneys are involved in the handling of major biochemical classes of metabolites. These metabolite levels capture a snap-shot of the metabolic profile of the individual, allowing for the potential identification of early biomarkers, and the monitoring of real-time kidney function. In this review, we describe the current status of the identification of blood/urine/faecal metabolic biomarkers in different entities of kidney diseases including: acute kidney injury, chronic kidney disease, renal transplant, diabetic nephropathy and other disorders.</p
Effect of heeled shoes on joint symptoms and knee osteoarthritis (OA) in older adults: a 5-year follow-up study
Get PDFObjective: our aims were to examine the effects of heeled shoes on incident knee OA and joint pain. Methods: we used longitudinal data from the Chingford 1000 Women Study (Chingford Study); a prospective cohort of women aged ≥50 years. Participants with musculoskeletal disorders and/or a history of knee-related injury/surgery were excluded. Participants were followed for up to 5-years for incident outcomes including; i) radiographic knee OA (RKOA) and ii) joint pain (feet, knees, hips and back). Footwear data including ever worn heels ≥2 inches and, daytime/evening hours (per week) spent wearing heeled shoes over five-decades (ages <20, 20-30, 30-40, >50 years) were available at Year 10 whilst knee radiographs and joint symptom data were also collected at Year 15. Cumulative time spent wearing heeled shoes was calculated for women reporting ever use of heeled shoes (≥2 inches). Multiple logistic regression was used to examine the relationship between exposures and outcomes (from years 10 to 15).Results: 356 women were eligible at Year 10 with the median (IQR) age 60 (56 to 65) years. Compared to non-use, ever use of heeled shoes (≥2 inches) was not associated with incident RKOA (1.35, 95% CI 0.56 to 3.27). No association was observed between increasing cumulative time spent wearing heels and incident outcomes. Conclusion: compared to the non-use of heeled shoes, ever use of heels (≥2 inches) was not associated with incident RKOA and incident joint symptoms, respectively. Further, increasing cumulative time spent wearing heels was not associated with any of our outcomes
Serum branched-chain amino acid to histidine ratio: a novel metabolomic biomarker of knee osteoarthritis
No full textObjective: There is a pressing need to develop reliable molecular biomarkers in osteoarthritis. The aim of the study was to identify novel serum biomarkers for osteoarthritis using a metabolomics approach. Methods: A two-stage study design was utilised. 123 knee osteoarthritis cases and 299 controls were selected from the TwinsUK cohort as a discovery sample. 76 knee osteoarthritic cases and 100 controls from the Chingford Study were used as replication. Knee osteoarthritis was defined as either radiographic, medically diagnosed or total knee joint replacement due to primary osteoarthritis. All the subjects were unrelated white women. Their serum samples were assessed for targeted metabolite profiling by electrosprary ionisation tandem mass spectrometry using the AbsoluteIDQ kit. 163 serum metabolites were assessed and their concentrations obtained. The ratios of metabolite concentrations as proxies for enzymatic reaction rates were calculated and tested for the association with knee osteoarthritis. Significance was assessed after adjustment for multiple testing (Bonferroni method) and potential confounders. Results: In the discovery stage, the authors identified 14 ratios significantly associated with knee osteoarthritis with p≤1.9 x 10⁻⁶. Two of these 14 ratios were successfully confirmed in the replication stage - the ratios of valine to histidine and xleucine to histidine, with p=0.002. The significance remained after adjustment for age and body mass index. Conclusion: This is the first serum-based metabolomic study of osteoarthritis in humans. The branched-chain amino acids to histidine ratio has potential clinical use as an osteoarthritis biomarker and shows the clinical potential of metabolomics
Contribution of heritability and epigenetic factors to skeletal muscle mass variation in UK twins
Get PDFContext: Skeletal muscle mass (SMM) is one of the major components of human body composition, with deviations from normal values often leading to sarcopenia.Objective: Our major aim was to conduct a genome-wide DNA methylation study in an attempt to identify potential genomic regions associated with SMM.Design: This was a mixed cross-sectional and longitudinal study.Setting: Community-based study.Participants: A total of 1550 middle-aged UK twin (monozygotic and dizygotic) twins, 297 of which were repeatedly measured participated in the study.Main Outcome Measure: Appendicular lean mass assessed using DXA technology, and MeDIP-seq DNA methylation profiling genome-wide were obtained from each individual.Results: Heritability estimate of SMM, with simultaneous adjustment for covariates obtained using variance decomposition analysis was h2=0.809±0.050. After quality control and analysis of longitudinal stability, the DNA methylation data comprised of 723,029 genomic sites, with positive correlations between repeated measurements (Rrepeated =0.114–0.905). Correlations between MZ and DZ twins were 0.51 and 0.38 at a genome-wide average, respectively and clearly increased with Rrepeated. Testing for DNA methylation association with SMM in 50 discordant MZ twins revealed 36,081 nominally significant results, of which the top-ranked 134 signals (P<0.01 and Rrepeated>0.40) were subjected to replication in the sample of 1,196 individuals. Seven SMM-methylation association signals replicated at a false discovery rate <0.1, and these were located in or near genes DNAH12, CAND1, CYP4F29P, ZFP64 which have previously been highlighted in muscle-related studies. Adjusting for age, smoking and blood cell heterogeneity did not alter significance of these associations.Conclusion: This epigenome-wide study, testing longitudinally stable methylation sites discovered and replicated a number of associations between DNA methylation at CpG loci and skeletal muscle mass. Four replicated signals were related to genes with potential muscle functions, suggesting that the methylome of whole blood may be informative of SMM variation<br/
Common STAT3 variants are not associated with obesity or insulin resistance in female twins
No full textJAMSHIDI, YALDA, THEODOSIOS KYRIAKOU, SAKINA B. GOOLJAR, LAURA J. COLLINS, CARL A. LANE, HAROLD SNIEDER, XIAOLING WANG, TIM D. SPECTOR, AND SANDRA D. O'DELL. Common STAT3 variants are not associated with obesity or insulin resistance in female twins. Obesity. 2007; 15:1634-1639. In animal models, STAT3 action in the hypothalamus and liver appears essential for normal body weight and glucose homeostasis in response to insulin. We hypothesized that variation in the STAT3 gene may be associated with body fat and/or insulin resistance in the general population. Five tagging SNPs spanning the STAT3 gene, rs8074524, rs2293152, rs2306580, rs6503695, and rs7211777 were genotyped in 2776 white female twins (mean age, 47.4 +/- 12.5 yrs) from the St Thomas' United Kingdom Adult Twin Registry (Twins UK). Minor allele frequencies were as follows: rs8074524 (0.19), rs2293152 (0.37), rs2306580 (0.06), rs6503695 (0.35), and rs7211777 (0.34). The minor allele of rs2293152 was associated with higher homeostasis model assessment index of insulin resistance (p = 0.013) in the full cohort and confirmed in sib-transmission/disequilibrium test (TDT): (p = 0.015; n = 60). However, there were no associations with fasting serum insulin or glucose or with obesity variables. Although defective STAT3 action results in obesity and insulin resistance in animal models, we failed to establish any indicative associations with common SNPs in this human study
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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