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| 12. |
- Ho, J. E., et al.
(författare)
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Clinical and genetic correlates of growth differentiation factor 15 in the community
- 2012
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 58:11, s. 1582-1591
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Growth differentiation factor 15(GDF15), a stress-responsive cytokine produced in cardiovascular cells under conditions of inflammation and oxidative stress, is emerging as an important prognostic marker in individuals with and without existing cardiovascular disease (CVD). We therefore examined the clinical and genetic correlates of circulating GDF15 concentrations, which have not been investigated collectively. METHODS: Plasma GDF15 concentrations were measured in 2991 participants in the Framingham Offspring Study who were free of clinically overt CVD (mean age, 59 years; 56% women). Clinical correlates of GDF15 were examined in multivariable analyses. We then conducted a genomewide association study of the GDF15 concentration that included participants in the Framingham Offspring Study and participants in the PIVUS (Prospective Investigation of the Vasculature in Uppsala Seniors) study. RESULTS: GDF15 was positively associated with age, smoking, antihypertensive treatment, diabetes, worse kidney function, and use of nonsteroidal antiinflammatory drugs (NSAIDs), but it was negatively associated with total cholesterol and HDL cholesterol. Clinical correlates accounted for 38% of interindividual variation in the circulating GDF15 concentration, whereas genetic factors accounted for up to 38% of the residual variability (h 2 = 0.38; P = 2.5 X 10 -11). We identified 1 locus of genomewide significance. This locus, which is on chromosome 19p13.11 and includes the GDF15 gene, is associated with GDF15 concentration (smallest P = 2.74 X 10 -32 for rs888663). Conditional analyses revealed 2 independent association signals at this locus (rs888663 and rs1054564), which were associated with altered cis gene expression in blood cell lines. CONCLUSIONS: In ambulatory individuals, both cardiometabolic risk factors and genetic factors play important roles in determining circulating GDF15 concentrations and contribute similarly to the overall variation.
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| 13. |
- Hunter, Ingrid, et al.
(författare)
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N-Terminal Pro-Atrial Natriuretic Peptide Measurement in Plasma Suggests Covalent Modification
- 2011
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Ingår i: Clinical Chemistry. - : American Association for Clinical Chemistry. - 0009-9147 .- 1530-8561. ; 57:9, s. 1327-1330
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The N-terminal fragment of cardiac-derived pro-B-type natriuretic peptide is a glycosylated polypeptide. It is unknown whether N-terminal proatrial natriuretic peptide (proANP) fragments are also covalently modified. We therefore evaluated the clinical performance of 2 distinctly different proANP assays on clinical outcome. METHODS: We examined 474 elderly patients with symptoms of heart failure presenting in a primary healthcare setting. Samples were analyzed with an automated immunoluminometric midregion proANP (MR-proANP) assay and a new processing-independent assay (PIA) developed in our laboratory. The results were compared with Bland-Altman plots, and clinical performance was assessed by generating ROC curves for different clinical outcomes. RESULTS: Despite linear regression results indicating a good correlation (r = 0.85; P less than 0.0001), the PIA measured considerably more proANP than the MR-proANP assay (mean difference, 663 pmol/L; SD, 478 pmol/L). In contrast, the clinical performances of the 2 assays [as assessed by the area under the ROC curve (AUC)] in detecting left ventricular dysfunction were similar [proANP PIA, 0.71 (95% CI, 0.63-0.79); MR-proANP assay, 0.74 (95% CI, 0.66-0.81); P = 0.32]. The prognostic ability to report cardiovascular mortality during a 10-year follow-up revealed AUC values of 0.66 (95% CI, 0.60-0.71) for the proANP PIA and 0.69 (95% CI, 0.63-0.74) for the MR-proANP assay (P = 0.08, for comparing the 2 assays). CONCLUSIONS: Our data suggest that N-terminal proANP fragments in patient plasma differ from the calibrator peptides used but that the difference does not affect ROC curves in an elderly cohort of patients with mild to moderate heart failure. We suggest that human N-terminal proANP fragments can be covalently modified.
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| 15. |
- Jiang, Jieying, et al.
(författare)
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Association of SRD5A2 variants and serum androstane-3alpha,17beta-diol glucuronide concentration in Chinese elderly men.
- 2010
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Ingår i: Clinical chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 56:11, s. 1742-9
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Tidskriftsartikel (refereegranskat)abstract
- Results of recent studies have demonstrated that genetic variants of the enzyme steroid 5α reductase type II (SRD5A2) are associated with serum concentrations of major androgen metabolites such as conjugates of androstane-3α,17β-diol-glucuronide (3α-diol-G). However, this association was not consistently found among different ethnic groups. Thus, we aimed to determine whether the association with SRD5A2 genetic variations exists in a cohort of healthy Chinese elderly men, by examining 2 metabolite conjugates: androstane-3α,l7β-diol-3-glucuronide (3α-diol-3G) and androstane-3α,17β-diol-17-glucuronide (3α-diol-17G).
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| 16. |
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| 17. |
- Leinenbach, Andreas, et al.
(författare)
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Mass spectrometry-based candidate reference measurement procedure for quantification of amyloid-β in cerebrospinal fluid.
- 2014
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Ingår i: Clinical chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 60:7, s. 987-94
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) amyloid-β (Aβ42) is a well-established biomarker for Alzheimer disease. Several immunoassays for Aβ42 exist but differ in absolute concentrations and may suffer from matrix interference, thereby hampering interlaboratory comparisons and the use of general cutoff levels. Together with the IFCC Working Group on CSF Proteins, we developed a candidate reference measurement procedure (RMP) for Aβ42.
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| 20. |
- Lund, Soren S., et al.
(författare)
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Agreement Between Fasting and Postprandial LDL Cholesterol Measured with 3 Methods in Patients with Type 2 Diabetes Mellitus
- 2011
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 57:2, s. 298-308
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: LDL cholesterol (LDL-C) is a modifiable cardiovascular disease risk factor. We used 3 LDL-C methods to study the agreement between fasting and postprandial LDL-C in type 2 diabetes (T2DM) patients. METHODS: We served 74 T2DM patients a standardized meal and sampled blood at fasting and 1.5, 3.0, 4.5, and 6.0 h postprandially. We measured LDL-C by use of modified beta quantification (MBQ), the Friedewald equation (FE), and a direct homogeneous assay (DA). We evaluated agreement using 95% limits of agreement (LOA) within +/- 0.20 mmol/L (+/- 7.7 mg/dL). RESULTS: LDL-C concentrations at all postprandial times disagreed with those at fasting for all methods. In 66 patients who had complete measurements with all LDL-C methods, maximum mean differences (95% LOA) in postprandial vs fasting LDL-C were -0.16 mmol/L (-0.51; 0.19) [-6.2 mg/dL (-19.7; 7.3)] with MBQ at 3 h; -0.36 mmol/L (-0.89; 0.17) [-13.9 mg/dL (-34; 6.6)] with FE at 4.5 h; and -0.24 mmol/L (-0.62; 0.05) [-9.3 mg/dL (-24; 1.9)] with DA at 6.0 h. In postprandial samples, FE misclassified 38% of patients (two-thirds of statin users) into lower Adult Treatment Panel III (ATP III) risk categories. Greater disagreement between fasting and postprandial LDL-C was observed in individuals with postprandial triglyceride concentrations >2.08 mmol/L (>184 mg/dL) and in women (interactions: P <= 0.038). CONCLUSIONS: Differences up to 0.89 mmol/L (34 mg/dL) between fasting and postprandial LDL-C concentrations, with postprandial LDL-C concentrations usually being lower, were found in T2DM by 3 different LDL-C methods. Such differences are potentially relevant clinically and suggest that, irrespective of measurement method, postprandial LDL-C concentrations should not be used to assess cardiovascular disease risk. (C) 2010 American Association for Clinical Chemistry
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