| 1. |
- 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. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 3. |
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| 4. |
- De La Vega Elena, Carlos D., et al.
(författare)
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A rare blood group: p phenotype
- 2009
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Ingår i: Medicina. - 1648-9144. ; 69:6, s. 651-654
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Tidskriftsartikel (refereegranskat)abstract
- A rare blood group: p phenotype. A rare blood group is usually defined as the absence of a high prevalence antigen or the absence of several antigens within a single blood group system. These individuals may develop clinically significant red cell antibodies to the high incidence red cell antigens they lack. A 33-year-old alloimmunized woman was referred to our center at the 12th week of her third pregnancy for evaluation and follow up. The laboratory work-up grouped her as belonging to "p" phenotype, associated with difficulties to find compatible blood for transfusion and a high incidence of recurrent miscarriage. At 36 weeks, a baby girl was born by induced labor due to fetal suffering. With a negative direct antiglobulin test but a positive elution test, she was in the neonatology ward for one week receiving luminotherapy. Homozygosity for a missense mutation at position 752 (c.752C > T) in the A4GALT gene was found to be responsible for the p phenotype. This mutation changes a proline to a leucine at codon 251 of the 4-alpha-galactosyltransferase. Recently, due to an imminent chirurgical intervention and the impossibility to have compatible blood available for transfusion. an autologous donation plan was designed to satisfy probable demand. This case showed the need for blood bank facilities capable to respond satisfactorily to these situations in Argentina. This would facilitate the storage of cryopreserved blood from individuals with rare blood groups for homologous use or to develop rare blood donors programs.
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| 5. |
- Sanchez-Vega, M., et al.
(författare)
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Studies of quadrupole collectivity in the γ -soft 106Ru
- 2008
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Ingår i: European Physical Journal A. - 1434-6001 .- 1434-601X. ; 35:2, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- Various alternative models were used to describe the structure of 106Ru . For example, the General Collective Model (GCM) predicts shape-coexistence for 106Ru with a spherical and a triaxial minimum and strongly mixed structures, while in the IBA-2 calculations, where 106Ru was considered as transitional from vibrational U(5) to γ -soft O(6) , no need was found to include the shape-coexisting configurations. In order to provide additional constraints on the model interpretations, we have applied the Advanced Time-Delayed (ATD) βγγ(t) method to measure the level lifetimes of the excited levels in 106Ru . The new results include the half-lives of T 1/2 = 183(3) ps and 7.5(30)ps for the 2+ 1 and 2+ 2 states, respectively.
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| 6. |
- Lu, R, et al.
(författare)
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Genetic associations of LYN with systemic lupus erythematosus
- 2009
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 10:5, s. 397-403
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Tidskriftsartikel (refereegranskat)abstract
- We targeted LYN, a src-tyosine kinase involved in B-cell activation, in case-control association studies using populations of European-American, African-American and Korean subjects. Our combined European-derived population, consisting of 2463 independent cases and 3131 unrelated controls, shows significant association with rs6983130 in a female-only analysis with 2254 cases and 2228 controls (P=1.1 x 10(-4), odds ratio (OR)=0.81 (95% confidence interval: 0.73-0.90)). This single nucleotide polymorphism (SNP) is located in the 5' untranslated region within the first intron near the transcription initiation site of LYN. In addition, SNPs upstream of the first exon also show weak and sporadic association in subsets of the total European-American population. Multivariate logistic regression analysis implicates rs6983130 as a protective factor for systemic lupus erythematosus (SLE) susceptibility when anti-dsDNA, anti-chromatin, anti-52 kDa Ro or anti-Sm autoantibody status were used as covariates. Subset analysis of the European-American female cases by American College of Rheumatology classification criteria shows a reduction in the risk of hematological disorder with rs6983130 compared with cases without hematological disorders (P=1.5 x 10(-3), OR=0.75 (95% CI: 0.62-0.89)). None of the 90 SNPs tested show significant association with SLE in the African American or Korean populations. These results support an association of LYN with European-derived individuals with SLE, especially within autoantibody or clinical subsets.
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| 7. |
- Sanchez-Vega, M., et al.
(författare)
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Studies of quadrupole collectivity in the γ -soft 106Ru
- 2008
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Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 35:2, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- Various alternative models were used to describe the structure of Ru-106. For example, the General Collective Model (GCM) predicts shape-coexistence for Ru-106 with a spherical and a triaxial minimum and strongly mixed structures, while in the IBA-2 calculations, where Ru-106 was considered as transitional from vibrational U(5) to gamma -soft O(6) , no need was found to include the shape-coexisting configurations. In order to provide additional constraints on the model interpretations, we have applied the Advanced Time-Delayed (ATD) beta gamma gamma(t) method to measure the level lifetimes of the excited levels in Ru-106 . The new results include the half-lives of T-1/2 = 183(3) ps and 7.5(30)ps for the 2(1)(+) and 2(1)(+) states, respectively.
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| 8. |
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| 9. |
- Delgado-Vega, Angelica M., et al.
(författare)
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Replication of the TNFSF4 (OX40L) promoter region association with systemic lupus erythematosus
- 2009
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 10:3, s. 248-253
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Tidskriftsartikel (refereegranskat)abstract
- The tumor necrosis factor ligand superfamily member 4 gene (TNFSF4) encodes the OX40 ligand (OX40L), a costimulatory molecule involved in T-cell activation. A recent study demonstrated the association of TNFSF4 haplotypes located in the upstream region with risk for or protection from systemic lupus erythematosus (SLE). To replicate this association, five single nucleotide polymorphisms (SNPs) tagging the previously associated haplotypes and passing the proper quality-control filters were tested in 1312 cases and 1801 controls from Germany, Italy, Spain and Argentina. The association of TNFSF4 with SLE was replicated in all the sets except Spain. There was a unique risk haplotype tagged by the minor alleles of the SNPs rs1234317 (pooled odds ratio (OR)=1.39, P=0.0009) and rs12039904 (pooled OR=1.38, P=0.0012). We did not observe association to a single protective marker (rs844644) or haplotype as the first study reported; instead, we observed different protective haplotypes, all carrying the major alleles of both SNPs rs1234317 and rs12039904. Association analysis conditioning on the haplotypic background confirmed that these two SNPs explain the entire haplotype effect. This first replication study confirms the association of genetic variation in the upstream region of TNFSF4 with susceptibility to SLE.
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| 10. |
- Orozco, Gisela, et al.
(författare)
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Association of STAT4 with rheumatoid arthritis : a replication study in three European populations
- 2008
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 58:7, s. 1974-1980
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This study was undertaken to investigate the previously reported association of the STAT4 polymorphism rs7574865 with rheumatoid arthritis (RA) in 3 different European populations from Spain, Sweden, and The Netherlands, comprising a total of 2,072 patients and 2,474 controls. METHODS: Three different cohorts were included in the study: 923 RA patients and 1,296 healthy controls from Spain, 273 RA patients and 285 healthy controls from Sweden, and 876 RA patients and 893 healthy controls from The Netherlands. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for the STAT4 single-nucleotide polymorphism rs7574865 using a TaqMan 5'-allele discrimination assay. The chi-square test was performed to compare allele and genotype distributions. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: We observed a significantly increased frequency of the minor T allele in RA patients compared with healthy controls in the Spanish population (24.8% versus 20.8%; P = 0.001, OR 1.26 [95% CI 1.09-1.45]). This association was confirmed in both the Swedish population (P = 0.03, OR 1.35 [95% CI 1.03-1.77]) and the Dutch population (P = 0.03, OR 1.45 [95% CI 1.21-1.73]). The overall P value for all 3 populations was 9.79 x 10(-6) (OR 1.25 [95% CI 1.13-1.37]). No association between rs7574865 and the presence of rheumatoid factor or anti-cyclic citrullinated peptide autoantibodies was observed. A meta-analysis of all published STAT4 associations revealed an OR of 1.25 (95% CI 1.19-1.33) (P = 1 x 10(-5)). CONCLUSION: Our findings indicate an association between the STAT4 polymorphism rs7574865 and RA in 3 different populations, from Spain, Sweden, and The Netherlands, thereby confirming previous data.
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