| 1. |
- Akiba, K., et al.
(author)
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LHC forward physics
- 2016
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In: Journal of Physics G: Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 43:11
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Journal article (peer-reviewed)
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| 2. |
- Liu, Kui, et al.
(author)
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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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In: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 119:4, s. 911-923
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Journal article (peer-reviewed)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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| 3. |
- Langefeld, Carl D., et al.
(author)
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Transancestral mapping and genetic load in systemic lupus erythematosus
- 2017
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
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| 4. |
- Namjou, B., et al.
(author)
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Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort
- 2011
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In: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 12:4, s. 270-279
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Journal article (peer-reviewed)abstract
- Systemic lupus erythematosus (SLE) is a prototypic autoimmune disorder with a complex pathogenesis in which genetic, hormonal and environmental factors have a role. Rare mutations in the TREX1 gene, the major mammalian 3'-5' exonuclease, have been reported in sporadic SLE cases. Some of these mutations have also been identified in a rare pediatric neurological condition featuring an inflammatory encephalopathy known as Aicardi-Goutieres syndrome (AGS). We sought to investigate the frequency of these mutations in a large multi-ancestral cohort of SLE cases and controls. A total of 40 single-nucleotide polymorphisms (SNPs), including both common and rare variants, across the TREX1 gene, were evaluated in similar to 8370 patients with SLE and similar to 7490 control subjects. Stringent quality control procedures were applied, and principal components and admixture proportions were calculated to identify outliers for removal from analysis. Population-based case-control association analyses were performed. P-values, false-discovery rate q values, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. The estimated frequency of TREX1 mutations in our lupus cohort was 0.5%. Five heterozygous mutations were detected at the Y305C polymorphism in European lupus cases but none were observed in European controls. Five African cases incurred heterozygous mutations at the E266G polymorphism and, again, none were observed in the African controls. A rare homozygous R114H mutation was identified in one Asian SLE patient, whereas all genotypes at this mutation in previous reports for SLE were heterozygous. Analysis of common TREX1 SNPs (minor allele frequency (MAF)>10%) revealed a relatively common risk haplotype in European SLE patients with neurological manifestations, especially seizures, with a frequency of 58% in lupus cases compared with 45% in normal controls (P = 0.0008, OR = 1.73, 95% CI = 1.25-2.39). Finally, the presence or absence of specific autoantibodies in certain populations produced significant genetic associations. For example, a strong association with anti-nRNP was observed in the European cohort at a coding synonymous variant rs56203834 (P = 2.99E-13, OR = 5.2, 95% CI = 3.18-8.56). Our data confirm and expand previous reports and provide additional support for the involvement of TREX1 in lupus pathogenesis. Genes and Immunity (2011) 12, 270-279; doi:10.1038/gene.2010.73; published online 27 January 2011
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| 5. |
- Lara-Cerón, Jesús A., et al.
(author)
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Ultrasound-assisted synthesis of organotin compounds and their application as luminescent dye in silk fibroin scaffolds
- 2020
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In: Inorganica Chimica Acta. - : Elsevier BV. - 0020-1693. ; 505
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Journal article (peer-reviewed)abstract
- In this work, we report the green synthesis of four luminescent organotin compounds 1–4 derived from amino acid Schiff bases (1: Naph-Trp-SnPh2, 2: Naph-Tyr-SnBu2, 3: Naph-Tyr-SnPh2, 4: Naph-Phe-SnPh2), obtained by ultrasound-assisted synthesis in short time (~20 min) and good yields (>95%). The molecular structure proposed in solution (1H and 119Sn NMR) was confirmed by X-ray diffraction study for compound 1 where the tin atom resides in trigonal bipyramid geometry. Luminescent silk fibroin scaffolds (SF 1–4) were elaborated with organotin compounds by freeze-drying technique. Photophysical properties of organotin compounds and scaffolds were obtained in solid state, observing bathochromic behaviors in tyrosine derived compounds, suggesting that the tyrosine produce supramolecular interactions across the –OH group that change the fluorescent properties. Scaffolds 1–4 were characterized by FTIR, XDR, TG/DTG, and SEM analysis. In addition, cytotoxic analysis of SF 1 presents high cellular viability, which could be applied as a scaffold in tissue engineering.
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| 6. |
- Sábio, Rafael M., et al.
(author)
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Near-Infrared Luminescence from Visible-Light-Sensitized Ruthenium(II)-Neodymium(III) Heterobimetallic Bridged Complexes Containing Alkoxy(silyl) Functional Groups
- 2020
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In: Journal of the Brazilian Chemical Society. - : Sociedade Brasileira de Quimica (SBQ). - 0103-5053 .- 1678-4790. ; 31:4, s. 694-702
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Journal article (peer-reviewed)abstract
- New infrared emitting d-f (ruthenium(II)–neodymium(III)) heterobimetallic complexes with alkoxy(silyl) functional groups have been prepared. Visible excitation evidenced energy transfer processes from the ruthenium(II) donor to neodymium(III) acceptors leading to infrared emission. Energy transfer rates (kEnT) and efficiency of energy transfer (ηEnT) are, respectively, 0.61 × 107 s-1 and 44% for RuL1–NdL3 complex. Larger values of kEnT (3.04 × 107 s-1) and ηEnT (84%) were detected for RuL2–NdL4 complex. RuL1–NdL3 and RuL2–NdL4 complexes were fully characterized by elementary analysis (EA), mass spectrometry (MS), Fourier transform infrared spectroscopy (FTIR) and Fourier transform Raman spectroscopy (FT-Raman). Total correlation spectroscopy (TOCSY1D), 1H{13C} heteronuclear single quantum correlation (HSQC) and 1H{13C} heteronuclear multiple bond correlation (HMBC) nuclear magnetic resonance (NMR) analyses were also carried out to characterize NdL3 and RuL1–NdL3 complexes. The presence of trialkoxysilyl-substituted ligands would allow further grafting onto any silica or silicated surface aiming at applications as new luminescent near infrared (NIR)-emitting biosensors or biomarkers.
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| 7. |
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| 8. |
- Löfgren, Sara E., et al.
(author)
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A 3 '-Untranslated Region Variant Is Associated With Impaired Expression of CD226 in T and Natural Killer T Cells and Is Associated With Susceptibility to Systemic Lupus Erythematosus
- 2010
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 62:11, s. 3404-3414
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Journal article (peer-reviewed)abstract
- Objective. Costimulatory receptor CD226 plays an important role in T cell activation, differentiation, and cytotoxicity. This study was undertaken to investigate the genetic association of CD226 with susceptibility to systemic lupus erythematosus (SLE) and to assess the functional implications of this association. Methods. Twelve tag single-nucleotide polymorphisms (SNPs) in CD226 were typed in 1,163 SLE patients and 1,482 healthy control subjects from Europe or of European ancestry. Analyses of association were performed by single-marker Cochran-Mantel-Haenszel meta-analysis, followed by haplotype analysis. Gene expression was analyzed by quantitative real-time polymerase chain reaction analyses of RNA from peripheral blood mononuclear cells, and by fluorescence-activated cell sorter analysis. To study the functional impact of the associated variants, luciferase reporter constructs containing different portions of the 3'-untranslated region (3'-UTR) of the gene were prepared and used in transfection experiments. Results. A 3-variant haplotype, rs763361; rs34794968; rs727088 (ATC), in the last exon of CD226 was associated with SLE (P = 1.3 x 10(-4), odds ratio 1.24, 95% confidence interval 1.11-1.38). This risk haplotype correlated with low CD226 transcript expression and low CD226 protein levels on the surface of CD4+ and CD8+ T cells and natural killer T (NKT) cells. NK cells expressed high levels of CD226, but this expression was independent of the haplotype. Reporter assays with deletion constructs indicated that only the presence of rs727088 could account for the differences in the levels of luciferase transcripts. Conclusion. This study identified an association of CD226 with SLE in individuals of European ancestry. These data support the importance of the 3'-UTR SNP rs727088 in the regulation of CD226 transcription both in T cells and in NKT cells.
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| 9. |
- Andersen, J. R., et al.
(author)
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Small-x phenomenology - Summary of the 3rd Lund small-x workshop in 2004
- 2006
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 48:1, s. 53-105
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Research review (peer-reviewed)abstract
- A third workshop on small-x physics, within the Small-x Collaboration, was held in Hamburg in May 2004 with the aim of overviewing recent theoretical progress in this area and summarizing the experimental status.
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| 10. |
- Ferreira, Vitor, et al.
(author)
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Modulation of hypothalamic AMPK phosphorylation by olanzapine controls energy balance and body weight
- 2022
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In: Metabolism. - : Elsevier. - 0026-0495 .- 1532-8600. ; 137
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Journal article (peer-reviewed)abstract
- Background: Second-generation antipsychotics (SGAs) are a mainstay therapy for schizophrenia. SGA-treated patients present higher risk for weight gain, dyslipidemia and hyperglycemia. Herein, we evaluated the effects of olanzapine (OLA), widely prescribed SGA, in mice focusing on changes in body weight and energy balance. We further explored OLA effects in protein tyrosine phosphatase-1B deficient (PTP1B-KO) mice, a preclinical model of leptin hypersensitivity protected against obesity. Methods: Wild-type (WT) and PTP1B-KO mice were fed an OLA-supplemented diet (5 mg/kg/day, 7 months) or treated with OLA via intraperitoneal (i.p.) injection or by oral gavage (10 mg/kg/day, 8 weeks). Readouts of the crosstalk between hypothalamus and brown or subcutaneous white adipose tissue (BAT and iWAT, respectively) were assessed. The effects of intrahypothalamic administration of OLA with adenoviruses expressing constitutive active AMPK alpha 1 in mice were also analyzed. Results: Both WT and PTP1B-KO mice receiving OLA-supplemented diet presented hyperphagia, but weight gain was enhanced only in WT mice. Unexpectedly, all mice receiving OLA via i.p. lost weight without changes in food intake, but with increased energy expenditure (EE). In these mice, reduced hypothalamic AMPK phosphorylation concurred with elevations in UCP-1 and temperature in BAT. These effects were also found by intrahypothalamic OLA injection and were abolished by constitutive activation of AMPK in the hypothalamus. Additionally, OLA i. p. treatment was associated with enhanced Tyrosine Hydroxylase (TH)-positive innervation and less sympathetic neuron-associated macrophages in iWAT. Both central and i.p. OLA injections increased UCP-1 and TH in iWAT, an effect also prevented by hypothalamic AMPK activation. By contrast, in mice fed an OLA-supplemented diet, BAT thermogenesis was only enhanced in those lacking PTP1B. Our results shed light for the first time that a threshold of OLA levels reaching the hypothalamus is required to activate the hypothalamus BAT/iWAT axis and, therefore, avoid weight gain. Conclusion: Our results have unraveled an unexpected metabolic rewiring controlled by hypothalamic AMPK that avoids weight gain in male mice treated i.p. with OLA by activating BAT thermogenesis and iWAT browning and a potential benefit of PTP1B inhibition against OLA-induced weight gain upon oral treatment.
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| 11. |
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| 12. |
- Martínez-Sánchez, Noelia, et al.
(author)
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Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
- 2017
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In: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 26:1, s. 212-229.e12
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Journal article (peer-reviewed)abstract
- Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.
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| 13. |
- Morales Salinas, Alberto, et al.
(author)
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Clinical Perspective on Antihypertensive Drug Treatment in Adults With Grade 1 Hypertension and Low-to-Moderate Cardiovascular Risk : An International Expert Consultation
- 2017
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In: Current problems in cardiology. - : Elsevier. - 0146-2806 .- 1535-6280. ; 42:7, s. 198-225
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Research review (peer-reviewed)abstract
- Hypertension is a leading risk factor for disease burden globally. An unresolved question is whether grade 1 hypertension (140-159/90-99 mm Hg) with low (cardiovascular mortality < 1% at 10 years) to moderate (cardiovascular mortality ≥ 1% and <5% at 10 years) absolute total cardiovascular risk (CVR) should be treated with antihypertensive agents. A virtual international consultation process was undertaken to summarize the opinions of select experts. After holistic analysis of all epidemiological, clinical, psychosocial, and public health elements, this consultation process reached the following consensus in hypertensive adults aged < 80 years: (1) The question of whether drug treatment in grade 1 should be preceded by a period of some weeks or months during which only lifestyle measures are recommended cannot be evidence based, but the consensus opinion is to have a period of lifestyle alone reserved only to patients with grade 1 "isolated" hypertension (grade 1 uncomplicated hypertension with low absolute total CVR, and without other major CVR factors and risk modifiers). (2) The initiation of antihypertensive drug therapy in grade 1 hypertension with moderate absolute total CVR should not be delayed. (3) Men ≥ 55 years and women ≥ 60 years with uncomplicated grade 1 hypertension should automatically be classified within the moderate absolute total CVR category, even in the absence of other major CVR factors and risk modifiers. (4) Statins should be considered along with blood-pressure lowering therapy, irrespective of cholesterol levels, in patients with grade 1 hypertensive with moderate CVR.
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| 14. |
- Sábio, Rafael M., et al.
(author)
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New insights towards mesoporous silica nanoparticles as a technological platform for chemotherapeutic drugs delivery
- 2019
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In: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 564, s. 379-409
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Research review (peer-reviewed)abstract
- Mesoporous silica nanoparticles (MSNs)displays interesting properties for biomedical applications such as high chemical stability, large surface area and tunable pores diameters and volumes, allowing the incorporation of large amounts of drugs, protecting them from deactivation and degradation processes acting as an excellent nanoplatform for drug delivery. However, the functional MSNs do not present the ability to transport the therapeutics without any leakage until reach the targeted cells causing side effects. On the other hand, the hydroxyls groups available on MSNs surface allows the conjugation of specific molecules which can binds to the overexpressed Enhanced Growth Factor Receptor (EGFR)in many tumors, representing a potential strategy for the cancer treatment. Beyond that, the targeting molecules conjugate onto mesoporous surface increase its cell internalization and act as gatekeepers blocking the mesopores controlling the drug release. In this context, multifunctional MSNs emerge as stimuli-responsive controlled drug delivery systems (CDDS)to overcome drawbacks as low internalization, premature release before to reach the region of interest, several side effects and low effectiveness of the current treatments. This review presents an overview of MSNs fabrication methods and its properties that affects drug delivery as well as stimuli-responsive CDDS for cancer treatment.
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| 15. |
- Sánchez, Elena, et al.
(author)
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Association of a CD24 Gene Polymorphism with Susceptibility to Systemic Lupus Erythematosus
- 2007
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In: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 56:9, s. 3080-3086
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Journal article (peer-reviewed)abstract
- Objective. To determine the potential role of the CD24 A57V gene polymorphism in systemic lupus erythematosus (SLE). Methods. We studied 3 cohorts of Caucasian patients and controls. The Spanish cohort included 696 SLE patients and 539 controls, the German cohort included 257 SLE patients and 317 controls, and the Swedish cohort included 310 SLE patients and 247 controls. The CD24 A57V polymorphism was genotyped by polymerase chain reaction, using a predeveloped TaqMan allele discrimination assay. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results. In the Spanish cohort there was a statistically significant difference in the distribution of the CD24 V allele between SLE patients and controls (OR 3.6 [95% CI 2.13-6.16], P < 0.0001). In addition, frequency of the CD24 V/V genotype was increased in SLE patients compared with controls (OR 3.7 [95% CI 2.16-6.34], P < 0.00001). We sought to replicate this association with SLE in a German population and a Swedish population. A similar trend was found in the German group. The CD24 V/V genotype and the CD24 V allele were more frequent in SLE patients than in controls, although this difference was not statistically significant. No differences were observed in the Swedish group. A meta-analysis of the Spanish and German cohorts demonstrated that the CD24 V allele has a risk effect in SLE patients (pooled OR 1.25 [95% Cl 1.08-1.46], P = 0.003). In addition, homozygosity for the CD24 V risk allele significantly increased the effect (pooled OR 2.1,9 [95% Cl 1.50-3.22], P = 0.00007). Conclusion. These findings suggest that the CD24 A57V polymorphism plays a role in susceptibility to SLE in a Spanish population.
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