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- Sandholm, Niina, et al.
(författare)
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New susceptibility loci associated with kidney disease in type 1 diabetes
- 2012
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Ingår i: PLOS Genetics. - San Francisco, USA : Public Library of Science, PLOS. - 1553-7390 .- 1553-7404. ; 8:9, s. e1002921-
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genomewide association studies (GWAS) of T1D DN comprising similar to 2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 x 10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 x 10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-beta 1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 x 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.
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- Brismar, T. B., et al.
(författare)
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GLUCOCORTICOIDS AND SARCOIDOSIS: A LONGITUDINAL STUDY ON THE EFFECTS ON CORTICAL AND TRABECULAR BONE
- 2015
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Ingår i: Sarcoidosis Vasculitis and Diffuse Lung Diseases. - : MATTIOLI 1885. - 1124-0490. ; 32:1, s. 63-69
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Tidskriftsartikel (refereegranskat)abstract
- Background: Glucocorticoid induced osteoporosis is a well-known side effect of glucocorticoid treatment. In sarcoidosis the impact on bone by glucocorticoid treatment is complex due to hormonal disturbances of calcium and vitamin-D, which by itself may cause bone loss. In this study we aimed to investigate the longitudinal impact of glucocorticoids on cortical and trabecular bone in patients with mild, recently diagnosed sarcoidosis.Methods: Ten patients (8 females; mean age 44 (+/- 13)) were studied during one year of glucocorticoid treatment. The assessment of mainly cortical to purely trabecular bone was made by dual X-ray absorptiometry (DXA) of the spine and hip, quantitative ultrasound of the calcaneus, and magnetic resonance relaxometry of the spine and calcaneus. Bone and hormonal measurements were performed at baseline, after 3, 6, and 12 months, and baseline, 3 weeks and 3 months, respectively.Results: DXA of the spine, decreased from baseline at 6 months (P=0.01). R2 of the calcaneus decreased with time (B: -3.6; P=0.03). In the females (n=8) there was a significant decrease in DXA of the spine when comparing 3 months and 6 months (P=0.03), and 3 months and 12 months (P=0.02) and a decrease in R2 of the calcaneus from baseline to 12 months (P=0.01). There was no change in hormonal levels.Conclusion: Treatment of initial mild sarcoidosis with dose tapered glucocorticoid therapy only mildly affects the final trabecular and cortical bone and hormone levels. Dose tapering is an important part in glucocorticoid therapy, likely contributing to the mild effects on bone observed in this study.
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