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Sökning: WFRF:(Mellström Dan 1945) > (2010-2014)

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1.
  • Moayyeri, Alireza, et al. (författare)
  • Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:11, s. 3054-3068
  • Tidskriftsartikel (refereegranskat)abstract
    • Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
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2.
  • Albertsson, Daniel M, 1957, et al. (författare)
  • Hip and fragility fracture prediction by 4-item clinical risk score and mobile heel BMD: a women cohort study
  • 2010
  • Ingår i: BMC Musculosceletal disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background One in four Swedish women suffers a hip fracture yielding high morbidity and mortality. We wanted to revalidate a 4-item clinical risk score and evaluate a portable heel bone mineral density (BMD) technique regarding hip and fragility fracture risk among elderly women. Methods In a population-based prospective cohort study we used clinical risk factors from a baseline questionnaire and heel BMD to predict a two-year hip and fragility fracture outcome for women, in a fracture preventive program. Calcaneal heel BMD was measured by portable dual X-ray laser absorptiometry (DXL) and compared to hip BMD, measured with stationary dual X-ray absorptiometry (DXA) technique. Results Seven women suffered hip fracture and 14 women fragility fracture/s (at hip, radius, humerus and pelvis) among 285 women; 60% having heel BMD ≤ -2.5 SD. The 4-item FRAMO (Fracture and Mortality) Index combined the clinical risk factors age ≥80 years, weight <60 kg, prior fragility fracture, and impaired rise-up ability. Women having 2-4 risk factors showed odds ratio (OR) for hip fracture of 5.9 and fragility fracture of 4.4. High risk group hip fracture risk was 2.8% annually compared to 0.5% for the low risk majority (69%). Heel BMD showed hip fracture OR of 3.1 and fragility fracture OR of 2.6 per SD decrease. For 30 DXA assessed participants mean hip BMD at -2.5 SD level corresponded to a lower BMD at the heel. Five of seven hip fractures occurred within a small risk group of 32 women, identified by high FRAMO Index + prior fragility fracture + heel T-score ≤-3.5 SD. Conclusions In a follow-up study we identified high risk groups for hip and fragility fracture with our plain 4-item risk model. Increased fracture risk was also related to decreasing heel BMD in calcaneal bone, measured with a mobile DXL technique. A combination of high FRAMO Index, prior fragility fracture, and very low BMD restricted the high risk group to 11%, among whom most hip fractures occurred (71%). These practical screening methods could eventually reduce hip fracture incidence by concentrating preventive resources to high fracture risk women.
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3.
  • Almqvist, Erik G., et al. (författare)
  • Factors influencing insulin sensitivity in patients with mild primary hyperparathyroidism before and after parathyroidectomy
  • 2012
  • Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 72:2, s. 92-99
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. Primary hyperparathyroidism (PHPT) is associated with cardiovascular disease. The aims of this study were to investigate lipid and glucose metabolism in mild PHPT, and to identify whether insulin sensitivity correlates with circulating levels of adiponectin, SHBG, and osteocalcin before and after parathyroidectomy (PTX). Materials and methods. Forty-five patients with PHPT were examined before and 1 year after PTX. Circulating levels of triglycerides, total cholesterol, HDL-cholesterol, insulin, glucose, adiponectin, SHBG, osteocalcin, and erythropoietin were measured. Results. At baseline, the mean serum levels of total cholesterol, LDL-cholesterol and triglycerides were above the upper reference limit or in the upper normal range, and insulin sensitivity was reduced as assessed using the HOMA index. One year after parathyroidectomy, serum lipids as well as HOMA index and erythropoietin were unchanged while adiponectin had increased (p < 0.05), and SHBG and osteocalcin had decreased (p < 0.05 and p < 0.0001, respectively). HOMA index correlated negatively with circulating levels of adiponectin, SHBG and osteocalcin. In multiple regression analysis SHBG was the most important predictor of insulin sensitivity, both pre- and postoperatively. Conclusion. Untreated mild PHPT is associated with a moderate derangement of lipid and glucose metabolism. As previously shown in population-based cohorts, insulin sensitivity is positively associated with circulating concentrations of adiponectin, SHBG and osteocalcin. One year after PTX, the mean level of adiponectin was increased, but the levels of SHBG and osteocalcin had decreased and the levels of serum lipids and the insulin sensitivity remained unchanged as compared with baseline.
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4.
  • Andersson, Niklas, 1970, et al. (författare)
  • A variant near the interleukin-6 gene is associated with fat mass in Caucasian men
  • 2010
  • Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 34:6, s. 1011-9
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Regulation of fat mass appears to be associated with immune functions. Studies of knockout mice show that endogenous interleukin (IL)-6 can suppress mature-onset obesity. OBJECTIVE: To systematically investigate associations of single nucleotide polymorphisms (SNPs) near the IL-6 (IL6) and IL-6 receptor (IL6R) genes with body fat mass, in support for our hypothesis that variants of these genes can be associated with obesity. DESIGN AND STUDY SUBJECTS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based cross-sectional study of 18- to 20-year-old men (n=1049), from the Gothenburg area (Sweden). Major findings were confirmed in two additional cohorts consisting of elderly men from the Osteoporotic Fractures in Men (MrOS) Sweden (n=2851) and MrOS US (n=5611) multicenter population-based studies. MAIN OUTCOME: The genotype distributions and their association with fat mass in different compartments, measured with dual-energy X-ray absorptiometry. RESULTS: Out of 18 evaluated tag SNPs near the IL6 and IL6R genes, a recently identified SNP rs10242595 G/A (minor allele frequency=29%) 3' of the IL6 gene was negatively associated with the primary outcome total body fat mass (effect size -0.11 standard deviation (s.d.) units per A allele, P=0.02). This negative association with fat mass was also confirmed in the combined MrOS Sweden and MrOS US cohorts (effect size -0.05 s.d. units per A allele, P=0.002). When all three cohorts were combined (n=8927, Caucasian subjects), rs10242595(*)A showed a negative association with total body fat mass (effect size -0.05 s.d. units per A allele, P<0.0002). Furthermore, the rs10242595(*)A was associated with low body mass index (effect size -0.03, P<0.001) and smaller regional fat masses. None of the other SNPs investigated in the GOOD study were reproducibly associated with body fat. CONCLUSIONS: The IL6 gene polymorphism rs10242595(*)A is associated with decreased fat mass in three combined cohorts of 8927 Caucasian men.
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5.
  • Carlzon, Daniel, et al. (författare)
  • Both Low and High Serum Insulin-like Growth Factor-I Levels Associate with Increased Risk of Cardiovascular Events in Elderly Men.
  • 2014
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Most previous prospective studies suggest that low serum insulin-like growth factor-I (IGF-I) associates with increased risk of cardiovascular disease (CVD) events while other studies suggest that high serum IGF-I associates with increased risk of CVD events. We tested the hypothesis that not only low, but also high, serum IGF-I associate with increased risk of CVD events in elderly men. Methods and Results: Serum IGF-I levels were measured in 2901 elderly men (aged 69 to 81 years) included in the prospective population-based MrOS-Sweden cohort. Data for CVD events were obtained from national Swedish registers with no loss of follow-up. During follow-up (median 5.1 yrs) 589 of the participants experienced a CVD event. The association between serum IGF-I and risk of CVD events was nonlinear, and restricted cubic spline Cox regression analysis revealed a U-shaped association between serum IGF-I levels and CVD events (p<0.01 for nonlinearity). Low as well as high serum IGF-I (quintile 1 or 5 vs. quintiles 2-4) significantly associated with increased risk for CVD events (hazard ratio (HR) = 1.25, 95% confidence interval (CI) 1.02-1.54; and HR = 1.35, 95% CI 1.10-1.66, respectively). These associations remained after adjustment for prevalent CVD and multiple risk factors. High serum IGF-I associated with increased risk of coronary heart disease (CHD) events but not with risk of cerebrovascular events. Conclusion: Both low and high serum IGF-I levels are risk markers for CVD events in elderly men. The association between high serum IGF-I and CVD events is mainly driven by CHD events.
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6.
  • Chan, Ruth, et al. (författare)
  • Association between serum 25-hydroxyvitamin D and psychological health in older Chinese men in a cohort study.
  • 2011
  • Ingår i: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 130:1-2, s. 251-259
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Few studies evaluated the association between vitamin D and psychological health in Chinese. This study examined these associations in Chinese older men in Hong Kong. METHODS: Baseline serum 25-hydroxyvitamin D (25OHD), depression and cognitive function were assessed in 939 community-dwelling Chinese men aged >65. Data on depression status at 4-year follow up was available in 629 men. Data were collected for confounding factors: demographics, number of diseases, smoking, alcohol use, body mass index, physical activity, mobility limitations, dietary intake, season of blood measurement, and serum parathyroid hormone level. Multivariate logistic regression analyses were performed with adjustments for confounding factors. RESULTS: An inverse association between serum 25OHD and baseline depression was observed. Men in the highest (>=92nmol/L) compared with lowest (<=63nmol/L) quartile of serum 25OHD had an adjusted odds ratio for depression of 0.46 (95% CI: 0.22-0.98, P(trend)=0.004). The association was more pronounced in low vitamin D season than in high vitamin D season. No association was observed between serum 25OHD and incident depression at 4years. Baseline cognitive impairment was not associated with serum 25OHD in all models. LIMITATIONS: Self-reported measure of depression and cognitive performance, the small number of incident depression at 4-year follow up and selection bias may affect the study validity. CONCLUSIONS: Serum 25OHD was inversely associated with depression at baseline and was not linked to baseline cognitive impairment and 4-year incident depression in Chinese older men. Future studies are warranted to evaluate these associations in populations with higher prevalence of vitamin D deficiency.
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7.
  • Chan, Ruth, et al. (författare)
  • Not All Elderly People Benefit From Vitamin D Supplementation with Respect to Physical Function: Results From the Osteoporotic Fractures in Men Study, Hong Kong.
  • 2012
  • Ingår i: Journal of the American Geriatrics Society. - : Wiley. - 1532-5415 .- 0002-8614. ; 60:2, s. 290-295
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To examine vitamin D status and its association with physical performance and muscle mass in older Chinese men. DESIGN: Cross-sectional and prospective cohort study design. SETTING: Hong Kong, People's of Republic of China. PARTICIPANTS: Nine hundred thirty-nine community-dwelling men aged 65 and older for cross-sectional analysis and 714 for longitudinal analysis. MEASUREMENTS: Baseline serum 25-hydroxyvitamin D (25OHD) was measured using a competitive radioimmunoassay kit. Baseline and 4-year physical performance measures (grip strength, 6-m walking speed, step length in a 6-m walk, time to complete five chair stands) were measured, and appendicular skeletal muscle mass (ASM) was assessed using dual-energy X-ray absorptiometry. Data were collected for confounding factors: demographic, number of diseases, smoking, alcohol use, body mass index, physical activity, diet, season of blood sampling, and serum parathyroid hormone (PTH) level. Multivariate regression analyses were performed with adjustments for confounding factors. RESULTS: Mean ± standard deviation serum 25OHD level of this sample of Chinese community-dwelling older men who had a high level of baseline physical function was 77.9 ± 20.5 nmol/L; 94.1% of participants had serum 25OHD levels of 50 nmol/L or greater. Median (interquartile range) serum PTH level was 4.1 pmol/L (3.1-5.5 pmol/L). After adjustment for potential confounding factors, serum 25OHD levels were not associated with baseline or 4-year change in physical performance measures and ASM. CONCLUSION: In Chinese older men who are vitamin D replete and have a high level of baseline physical function, vitamin D may not have an important role in physical function and muscle mass.
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8.
  • Chan, R, et al. (författare)
  • Serum 25-hydroxyvitamin D and parathyroid hormone levels in relation to blood pressure in a cross-sectional study in older Chinese men.
  • 2012
  • Ingår i: Journal of human hypertension. - : Springer Science and Business Media LLC. - 1476-5527 .- 0950-9240. ; 26:1, s. 20-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Vitamin D status, parathyroid hormone (PTH) level and their associations with blood pressure in Chinese population are unknown. This study examined these associations in older Chinese men. Blood pressure, serum 25-hydroxyvitamin D (25OHD) and PTH was measured in 939 community-dwelling Chinese men aged 65 years and older. Linear regression analyses were performed with adjustments for age, body mass index, education, season of measurement, medication use, self-reported history of stroke and Parkinson's disease, and other lifestyle factors. In either crude or adjusted models, serum 25OHD was not associated with blood pressure, whereas increasing PTH levels was associated with higher blood pressure. Men in the highest quartile of serum PTH level had a mean difference of 3.4 mm Hg and 2.8 mm Hg higher in as systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively, than men in the lowest quartile of serum PTH level (P(trend)=0.019 for SBP and <0.001 for DBP). In conclusion, the findings support an association between serum PTH and blood pressure, but not for serum 25OHD in older Chinese men whose vitamin D status is optimal. The lack of association between serum 25OHD and blood pressure may possibly because of the relatively high serum 25OHD levels of the study sample.
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10.
  • Coviello, Andrea D, et al. (författare)
  • A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.
  • 2012
  • Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 8:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8×10(-106)), PRMT6 (rs17496332, 1p13.3, p = 1.4×10(-11)), GCKR (rs780093, 2p23.3, p = 2.2×10(-16)), ZBTB10 (rs440837, 8q21.13, p = 3.4×10(-09)), JMJD1C (rs7910927, 10q21.3, p = 6.1×10(-35)), SLCO1B1 (rs4149056, 12p12.1, p = 1.9×10(-08)), NR2F2 (rs8023580, 15q26.2, p = 8.3×10(-12)), ZNF652 (rs2411984, 17q21.32, p = 3.5×10(-14)), TDGF3 (rs1573036, Xq22.3, p = 4.1×10(-14)), LHCGR (rs10454142, 2p16.3, p = 1.3×10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7×10(-08)), and UGT2B15 (rs293428, 4q13.2, p = 5.5×10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5×10(-08), women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ∼15.6% and ∼8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
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