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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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- Naranjo, A., et al.
(författare)
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Smokers and non-smokers with rheumatoid arthritis have similar clinical status : data from the multinational QUEST-RA database
- 2010
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Ingår i: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 28:6, s. 820-827
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. Methods The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RE), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as "never smoked", "currently smoking" and "former smokers". Patient groups with different smoking status were compared for demographic and RA measures. Results Among the 7,307 patients with smoking data available, status as "never smoked," "current smoker" and "former smoker" were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32; 1.17-1.48, p<0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41; 1.24-1.59, p<0.001). The percentage of patients with erosive arthritis and extra-articular disease was similar in all smoking categories. Mean DAS28 was 4.4 (SD 1.6) in non-smokers vs. 4.0 (SD 1.6) in those who had ever smoked. However, when adjusted by age, sex, disease duration, and country gross domestic product, only ESR remained significantly different among Core Data Set measures (mean 31.7mm in non-smokers vs. 26.8mm in ever smoked category). Conclusion RA patients who had ever smoked were more likely to have RF and nodules, hut values for other clinical status measures were similar in all smoking categories (never smoked, current smokers and former smokers).
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- Ahola, Virpi, et al.
(författare)
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The Glanville fritillary genome retains an ancient karyotype and reveals selective chromosomal fusions in Lepidoptera
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4737-
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have reported that chromosome synteny in Lepidoptera has been well conserved, yet the number of haploid chromosomes varies widely from 5 to 223. Here we report the genome (393 Mb) of the Glanville fritillary butterfly (Melitaea cinxia; Nymphalidae), a widely recognized model species in metapopulation biology and eco-evolutionary research, which has the putative ancestral karyotype of n = 31. Using a phylogenetic analyses of Nymphalidae and of other Lepidoptera, combined with orthologue-level comparisons of chromosomes, we conclude that the ancestral lepidopteran karyotype has been n = 31 for at least 140 My. We show that fusion chromosomes have retained the ancestral chromosome segments and very few rearrangements have occurred across the fusion sites. The same, shortest ancestral chromosomes have independently participated in fusion events in species with smaller karyotypes. The short chromosomes have higher rearrangement rate than long ones. These characteristics highlight distinctive features of the evolutionary dynamics of butterflies and moths.
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- Aksela, S., et al.
(författare)
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Accurate free atom-solid binding energy shifts for Au and Ag
- 2012
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Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - : Elsevier BV. - 0368-2048. ; 185:8-9, s. 273-277
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Tidskriftsartikel (refereegranskat)abstract
- Binding energy shifts between atomic and solid states have been observed with improved accuracy for All 4f and Ag 3d core levels applying a simultaneous measurement method. Also the 3d photoelectron spectrum and binding energies of free Ag atoms have been observed for the first time. New values determined as free atom to bulk solid shifts deviate considerably from previous estimate for Au but agree reasonably well for Ag. The valence bands were also found to shift rather accurately by the same amount as the core levels. (C) 2012 Published by Elsevier B.V.
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- Natunen, Teemu, et al.
(författare)
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Elucidation of the BACE1 Regulating Factor GGA3 in Alzheimer's Disease
- 2013
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 37:1, s. 217-232
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Tidskriftsartikel (refereegranskat)abstract
- Golgi-localized gamma-ear-containing ADP-ribosylation factor-binding protein (GGA3) is a central regulator of trafficking and degradation of BACE1 (beta-site A beta PP-cleaving enzyme), the rate-limiting enzyme in the production of amyloid-beta (A beta) in Alzheimer's disease (AD). Here, we assessed the potential role of GGA3 in AD pathogenesis using independent neuropathological, case-control, and family-based human sample cohorts. Increased BACE1 levels coincided with decreased GGA3 levels and with elevated phosphorylation status of eIF2 alpha-Ser51 in the temporal cortex of AD patients as compared to age-matched controls. Severity of the disease did not alter mRNA or protein levels of GGA3 in the inferior temporal cortex of AD patients, while a positive correlation between GGA3 and the levels of total, but not phosphorylated, tau was observed. Genetically, we did not observe consistent evidence for association between AD risk and common GGA3 polymorphisms across a number of independent sample cohorts. However, a nominally significant association was observed with rs2242230 (p < 0.05) among the Finnish case-control cohort. Accordingly, mRNA and protein levels of GGA3 in the inferior temporal cortex of AD patients did not significantly correlate with rs2242230 genotype status. While the present study indicates that GGA3 is involved in the cellular processes relevant for AD pathogenesis, the genetic data do not support the idea that common GGA3 polymorphisms would contribute to AD risk.
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