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- Koettgen, Anna, et al.
(författare)
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Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:2, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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- Ljunggren, Stefan, et al.
(författare)
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Changes in Human Liportein Composition in Patients with Acute Coronary Syndrome
- 2011
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Ingår i: Atherosclerosis Supplements. - : Elsevier. - 1567-5688 .- 1878-5050. ; 12:1, s. 14-14
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The protein composition of lipoproteins may serve as biomarkers or reveal underlying mechanisms during different states of disease. Here we have analysed the protein composition of LDL and HDL from patients with acute coronary syndrome (ACS) and patients receiving statins after previous ACS. Plasma samples were obtained from males, namely 12 healthy donors, 9 patients with ACS and 7 stable patients receiving statin treatment after previous ACS. LDL and HDL were isolated by two-step density ultracentrifugation. LDL proteins were analysed with two-dimensional gel electrophoresis and mass spectrometry. Paraoxonase 1 (PON-1) in HDL was analyzed with SDSPAGE/Western Blot.Concentrations of apo A-IV, a1-antitrypsin and transthyretin were significantly increased (P < 0.05) in LDL from patients with ACS compared to healthy controls. In patients receiving statins, a1-antitrypsin remained increased while serum amyloid A4 was decreased. By western blot analysis, a non-significant increase in PON-1 was found in HDL from patients with ACS. Interestingly, a truncated form of PON-1 was detected in all patients with ACS but not in any of the controls.In conclusion, we confirm previous findings that LDL-associated transthyretin is a possible biomarker of myocardial infarction. Moreover, the increased concentration of the inflammatory marker a1-antitrypsin in LDL from both ACS patients and stable patients after ACS indicate that the enrichment does not only reflect an acute phase response. The presence of a truncated form of the antioxidant protein PON-1 in HDL may explain previous findings showing increased amounts but lower activity of PON-1 in patients with ACS.
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