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Sökning: WFRF:(O'Neill Terence W.) > (2010-2014) > Wu Frederick C W

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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.
  • Bentmar Holgersson, Magdalena, et al. (författare)
  • Androgen receptor polymorphism dependent variation in prostate specific antigen concentrations of European men.
  • 2014
  • Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 23:10, s. 2048-2056
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Androgens acting via the androgen receptor (AR) stimulate production of prostate specific antigen (PSA), which is a clinical marker of prostate cancer (PCa). Since genetic variants in the AR may have a significant impact on the risk of being diagnosed with PCa, the aim was to investigate if AR-variants were associated with the risk of having PSA above clinically used cut-off thresholds of 3 or 4 ng/mL in men without PCa. Methods Men without PCa history (n=1744) were selected from the European Male Ageing Study (EMAS) cohort of 40-80 year old men from 8 different European centers. Using linear and logistic regression models, with age and center as covariates, we investigated whether AR-variants (CAG repeat-length and/or SNP genotype) were associated with having serum PSA concentrations above 3 or 4 ng/mL, which often are set as cut-off concentrations for further investigation of PCa. Results Carriers of the SNP rs1204038 A-allele (16% of the men) were more likely to have PSA>3 and 4 ng/mL (OR; 95%CI 1.65; 1.13-2.40 and 1.87; 1.18-2.96, respectively) than G-allele carriers. They also had shorter CAG-repeats (median 20 vs. 23, p<0.0005), but CAG repeat length per se did not affect the PSA concentrations. Conclusion The A-allele of the SNP rs1204038 gives a 65% higher risk of having PSA above 3 ng/mL than the G-allele in men without PCa, and thereby an increased risk of being referred for further examination on suspicion of PCa. Impact Serum PSA as a clinical marker could be improved by adjustment for AR-genotype.
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3.
  • Boonen, Steven, et al. (författare)
  • Influence of bone remodelling rate on quantitative ultrasound parameters at the calcaneus and DXA BMDa of the hip and spine in middle-aged and elderly European men: the European Male Ageing Study (EMAS)
  • 2011
  • Ingår i: European Journal of Endocrinology. - 1479-683X. ; 165:6, s. 977-986
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To assess the influence of sex hormones on markers of bone turnover and to explore the association between these markers and bone health in middle-aged and elderly European men. Design: A cross-sectional population-based survey. Methods: Men aged 40-79 years were recruited from population registers in eight European centres. Subjects completed a postal questionnaire which included questions concerning lifestyle and were invited to undergo quantitative ultrasound (QUS) of the calcaneus and to provide a fasting blood sample from which the bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (beta C-terminal cross-linked telopeptide (beta-cTX)), total testosterone, total oestradiol (E-2), sex hormone-binding globulin (SHBG) and insulin-like growth factor 1 (IGF1) were measured. Dualenergy X-ray absorptiometry (DXA) of the hip and lumbar spine was performed in two centres. Results: A total of 3120, mean age 59.9 years (S.D. = 11.0) were included. After adjustment for centre, age, height, weight, lifestyle factors, season and other hormones, total and free E-2 were negatively associated with beta-cTX but not P1NP while SHBG, IGF1 and parathyroid hormone (PTH) were positively associated with both beta-cTX and P1NP. Total or free testosterone was not independently associated with either bone marker. After the same adjustments, higher levels of both bone markers were significantly associated with lower QUS parameters and lower DXA-assessed bone density at the total hip and lumbar spine. Conclusions: E-2, SHBG, IGF1 and PTH contribute significantly to the regulation/rate of bone turnover in middle-aged and older European men. Higher rates of bone remodelling are negatively associated with male bone health.
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4.
  • Corona, Giovanni, et al. (författare)
  • Age-Related Changes in General and Sexual Health in Middle-Aged and Older Men: Results from the European Male Ageing Study (EMAS)
  • 2010
  • Ingår i: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6109 .- 1743-6095. ; 7:4, s. 1362-1380
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction. Limited information is available concerning the general and sexual health status of European men. Aim. To investigate the age-related changes in general and sexual health in middle-aged and older men from different countries of the European Union. Methods. This is a cross-sectional multicenter survey performed on a sample of 3,369 community-dwelling men aged 40-79 years old (mean 60 +/- 11 years). Subjects were randomly selected from eight European centers including centers from nontransitional (Florence [Italy], Leuven [Belgium], Malmo [Sweden], Manchester [United Kingdom], Santiago de Compostela [Spain]) and transitional countries (Lodz [Poland], Szeged [Hungary], Tartu [Estonia]). Main Outcome Measures. Different parameters were evaluated including the Beck's Depression Inventory for the quantification of depressive symptoms, the Short Form-36 Health Survey for the assessment of the quality of life (QoL), the International Prostate Symptom Score for the evaluation of lower urinary tract symptoms, and the European Male Ageing Study sexual function questionnaire for the study of sexual function. Results. More than 50% of subjects reported the presence of one or more common morbidities. Overall, hypertension (29%), obesity (24%), and heart diseases (16%) were the most prevalent conditions. Around 30% of men reported erectile dysfunction (ED) and 6% reported severe orgasmic impairment, both of which were closely associated with age and concomitant morbidities. Only 38% of men reporting ED were concerned about it. Furthermore, concern about ED increased with age, peaking in the 50-59 years age band, but decreased thereafter. Men in transitional countries reported a higher prevalence of morbidities and impairment of sexual function as well as a lower QoL. Conclusion. Sexual health declined while concomitant morbidities increased in European men as a function of age. The burden of general and sexual health is higher in transitional countries, emphasizing the need to develop more effective strategies to promote healthy aging for men in these countries. Corona G, Lee DM, Forti G, O'Connor DB, Maggi M, O'Neill TW, Pendleton N, Bartfai G, Boonen S, Casanueva FF, Finn JD, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Lean MEJ, Punab M, Silman AJ, Vanderschueren D, Wu FCW, and EMAS Study Group. Age-related changes in general and sexual health in middle-aged and older men: Results from the European Male Ageing Study (EMAS). J Sex Med 2010;7:1362-1380.
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5.
  • Han, Thang S., et al. (författare)
  • Impaired quality of life and sexual function in overweight and obese men: the European Male Ageing Study
  • 2011
  • Ingår i: European Journal of Endocrinology. - 1479-683X. ; 164:6, s. 1003-1011
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Few published data link overweight and obesity with measures of quality of life (QoL) including sexual health in men. Objective: To assess the association of overweight/obesity with impairment of physical and psychological QoL and sexual functions in men. Design and setting: Cross-sectional, multicentre survey of 3369 community-dwelling men aged 40-79 (mean +/- S.D., 60 +/- 11) years randomly selected from eight European centres. Outcomes: Adiposity was assessed by body mass index (BMI) and waist circumference (WC), QoL and functional impairments by physical and psychological function domains of the Short Form-36 questionnaire, Beck's Depression Inventory and the European Male Ageing Study sexual function questionnaire. Results: Complete data on sexual activities and erectile function were available in 2734 (92%) and 3193 (95%) of the participants respectively. From the population studied, 814 men were obese (BMI >= 30 kg/m(2)) and 1171 had WC >= 102 cm, 25% of all men were unable to do vigorous activity and 2-13% reported depressive symptoms. Symptoms of sexual dysfunction ranged between 22% (low sexual desire) and 40% (infrequent morning erections) of the participants. Among obese men with both BMI >= 30 kg/m(2) and WC >= 102 cm, at least one symptom of impaired physical, psychological and sexual function was reported by 41, 43 and 73% of the participants respectively. Compared with the reference group of non-obese men (BMI < 30 kg/m(2) and WC < 102cm), men with BMI >= 30 kg/m(2) and WC >= 102 cm more frequently reported at least one symptom of impaired physical function (odds ratio (OR)=2.67; confidence interval (CI): 2.07-3.45, P < 0.001), impaired psychological function (OR=1.48; CI: 1.14-1.90, P < 0.01) and impaired sexual function (OR=1.45; CI: 1.14-1.85, P < 0.01). These functional impairments were also more prevalent in men who had WC >= 102 cm even with BMI < 30 kg/m(2), but those with BMI >= 30 kg/m(2) and WC < 102 cm generally did not suffer from increased impaired physical or sexual health. Men with high BMI and WC were at even greater likelihood of having a composite of two or more or three or more symptoms compared with those with normal BMI and WC. Conclusions: Men with high WC, including those who are 'non-obese' with BMI < 30 kg/m(2), have poor QoL with symptoms of impaired physical, psychological and sexual functions. Health promotion to improve QoL should focus on prevention of obesity and central fat accumulation.
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6.
  • Holliday, Kate L., et al. (författare)
  • The ESR1 (6q25) Locus Is Associated with Calcaneal Ultrasound Parameters and Radial Volumetric Bone Mineral Density in European Men
  • 2011
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor alpha gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMDa) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men. Methods: Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression. Results: 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMDa, a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMDa and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness. Conclusions: Our data replicate previous associations found between SNPs in the 6q25 locus and BMDa at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.
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7.
  • Huhtaniemi, Ilpo T., et al. (författare)
  • Comparison of serum testosterone and estradiol measurements in 3174 European men using platform immunoassay and mass spectrometry; relevance for the diagnostics in aging men
  • 2012
  • Ingår i: European Journal of Endocrinology. - 1479-683X. ; 166:6, s. 983-991
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The limitations of serum testosterone and estradiol (E-2) measurements using nonextraction platform immunoassays (IAs) are widely recognized. Switching to more specific mass spectrometry (MS)-based methods has been advocated, but directly comparative data on the two methods are scarce. Methods: We compared serum testosterone and E-2 measurements in a large sample of middle-aged/elderly men using a common platform IA and a gas chromatography (GC)-MS method, in order to assess their limitations and advantages, and to diagnose male hypogonadism. Of subjects from the European Male Aging Study (n = 3174; age 40-79 years), peripheral serum testosterone and E-2 were analyzed using established commercial platform IAs (Roche Diagnostics E170) and in-house GC MS methods. Results: Over a broad concentration range, serum testosterone concentration measured by IA and MS showed high correlation (R=0.93, P<0.001), which was less robust in the hypogonadal range (<11 nmol/l; R=0.72, P<0.001). The IA/MS correlation was weaker in E-2 measurements (R=0.32, P<0.001, at E-2 <40.8 pmol/l, and R=0.74, P<0.001, at E-2 >40.8 pmol/l). Using MS as the comparator method, IA ascertained low testosterone compatible with hypogonadism (<11 nmol/l), with 75% sensitivity and 96.3% specificity. The same parameters with IA for the detection of low E-2 (<40.7 pmol/l) were 13.3 and 99.3%, and for high E-2 (>120 pmol/l) 88.4 and 88.6%. Conclusion: A validated platform IA is sufficient to detect subnormal testosterone concentrations in the diagnosis of male hypogonadism. The IA used for E-2 measurements showed poor correlation with MS and may only be suitable for the detection of high E-2 in men.
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8.
  • Huhtaniemi, Ilpo T, et al. (författare)
  • Effect of Polymorphisms in Selected Genes Involved in Pituitary-Testicular Function on Reproductive Hormones and Phenotype in Aging Men.
  • 2010
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 1898-1908
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Polymorphisms in genes involved in regulation, biosynthesis, metabolism, and actions of testicular sex hormones may influence hormone balance and phenotype of aging men. Objective: We investigated the relationships between polymorphisms in genes related to pituitary-testicular endocrine function and health status. Design and Setting: Using cross-sectional baseline data, we conducted a multinational prospective cohort observational study consisting of a population survey of community-dwelling men. Participants: A total of 2748 men, aged 40-79 (mean +/- SD, 60.2 + 11.2) yr, were randomly recruited from eight European centers. Forty-three polymorphisms were genotyped in the following genes: androgen receptor (AR), estrogen receptor-alpha and -beta (ESR1 and ESR2), steroid 5alpha-reductase type II (SRD5A2), 17alpha-hydroxylase/17,20-lyase (CYP17A1), aromatase (CYP19A1), sex hormone-binding globulin (SHBG), LH beta-subunit (LHB), and LH receptor (LHCGR). Main Outcome Measures: We measured the associations between gene polymorphisms and endocrine, metabolic, and phenotypic parameters related to aging and sex hormone action. Results: Several polymorphisms in SHBG, ESR2, AR, CYP19A1, and LHB were significantly associated with circulating levels of SHBG, LH, total, free, and bioavailable testosterone and estradiol, the LH x testosterone product, and indices of insulin sensitivity. Apart from several previously reported associations between genes affecting estrogen levels and heel ultrasound parameters, no associations existed between polymorphisms and nonhormonal variables (anthropometry, blood lipids, blood pressure, hemoglobin, prostate symptoms, prostate-specific antigen, sexual dysfunction, cognition). Conclusion: In aging men, polymorphisms in genes related to the pituitary-testicular endocrine function significantly influence circulating LH, testosterone, and estradiol levels, but the downstream effects may be too small to influence secondary phenotypic parameters.
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9.
  • Lee, David M., et al. (författare)
  • Association of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone with mortality among middle-aged and older European men
  • 2014
  • Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 1468-2834 .- 0002-0729. ; 43:4, s. 528-535
  • Tidskriftsartikel (refereegranskat)abstract
    • Setting: prospective cohort analysis within the European Male Ageing Study. Participants: 2,816 community-dwelling men aged 40-79 years at baseline. Methods: Cox regression was used to examine the association of all-cause mortality with 25(OH)D, 1,25(OH)(2)D and PTH; cardiovascular and cancer mortality were modelled using competing-risks regression. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CIs) for Cox models; sub-hazard ratios (SHR) and 95% CIs for competing-risks models. Results: a total of 187 men died during a median of 4.3 years of follow-up. Serum levels of 25(OH)D (per 1 SD decrease: HR = 1.45; 95% CI = 1.16, 1.81) and 1,25(OH)(2)D (per 1 SD decrease: HR = 1.20; 95% CI = 1.00, 1.44) were associated with an increased risk of all-cause mortality after adjusting for age, centre, smoking, self-reported morbidities, physical activity and functional performance. Only levels of 25(OH)D < 25 nmol/l predicted cancer mortality (SHR = 3.33; 95% CI = 1.38, 8.04). Conclusion: lower 25(OH)D and 1,25(OH)(2)D levels independently predicted all-cause mortality in middle-aged and older European men. Associations with cancer mortality were only observed among men with very low levels of 25(OH)D. These associations were only partially explained by the range of adverse health and lifestyle factors measured here.
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10.
  • Lee, David M., et al. (författare)
  • Association of hypogonadism with vitamin D status: the European Male Ageing Study
  • 2012
  • Ingår i: European Journal of Endocrinology. - 1479-683X. ; 166:1, s. 77-85
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Interrelationships between hormones of the hypothalamic-pituitary-testicular (HPT) axis, hypogonadism, vitamin D and seasonality remain poorly defined. We investigated whether HPT axis hormones and hypogonadism are associated with serum levels of 25-hydroxyvitamin D (25(OH)D) in men. Design and methods: Cross-sectional survey of 3369 community-dwelling men aged 40-79 years in eight European centres. Testosterone (T), oestradiol (E(2)) and dihydrotestosterone were measured by gas chromatography-mass spectrometry; LH, FSH, sex hormone binding globulin (SHBG), 25(OH)D and parathyroid hormone by immunoassay. Free T was calculated from total T, SHBG and albumin. Gonadal status was categorised as eugonadal (normal T/LH), secondary (low T, low/normal LH), primary (low T, elevated LH) and compensated (normal T, elevated LH) hypogonadism. Associations of HPT axis hormones with 25(OH)D were examined using linear regression and hypogonadism with vitamin D using multinomial logistic regression. Results: In univariate analyses, free T levels were lower (P=0.02) and E(2) and LH levels were higher (P<0.05) in men with vitamin D deficiency (25(OH)D <50 nmol/l). 25(OH)D was positively associated with total and free T and negatively with E(2) and LH in age- and centre-adjusted linear regressions. After adjusting for health and lifestyle factors, no significant associations were observed between 25(OH)D and individual hormones of the HPT axis. However, vitamin D deficiency was significantly associated with compensated (relative risk ratio (RRR)=1.52, P=0.03) and secondary hypogonadism (RRR=1.16, P=0.05). Seasonal variation was only observed for 25(OH)D (P<0.001). Conclusions: Secondary and compensated hypogonadism were associated with vitamin D deficiency and the clinical significance of this relationship warrants further investigation.
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