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- Liu, Kui, et al.
(författare)
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Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans
- 2009
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 119:4, s. 911-923
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Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.
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| 2. |
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| 3. |
- Zhang, L, et al.
(författare)
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Blood lipid levels in relation to glucose status in seven populations of Asian origin without a prior history of diabetes : the DECODA study.
- 2009
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 25:6, s. 549-557
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dyslipidaemia commonly coexists with diabetes. We investigated the association of lipid profiles with glucose levels in populations of Asian origin without a prior history of diabetes. METHODS: Cross-sectional data of 10,374 men and 12,552 women aged 30-74 years from 14 cohorts, representing seven populations of Asian origin were jointly analysed. Multivariable adjusted linear regression analyses with standardized regression coefficients (beta) were performed to estimate relationships between lipids and plasma glucose. RESULTS: Within each glucose category, fasting plasma glucose (FPG) levels were correlated with increasing levels of triglycerides (TGs), total cholesterol (TC), TC to high-density lipoprotein (HDL) ratio and non-HDL cholesterol (non-HDL-C) (p < 0.05 in most of the ethnic groups) and inversely associated with HDL-C (p < 0.05 in some, but not all, of the populations). The association of lipids with 2-h plasma glucose (2hPG) followed a similar pattern as that for the FPG, except that an inverse relationship between HDL-C and glucose was more commonly observed for 2hPG than for FPG among different ethnic groups. CONCLUSIONS: Hyperglycaemia is associated with adverse lipid profiles in Asians without a prior history of diabetes. The 2hPG appears to be more closely associated with lipid profiles than does FPG. When assessing the risk of cardiovascular disease, the association of the dyslipidaemia with intermediate hyperglycaemia needs to be considered.
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