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Alarcón-Riquelme, Marta E.
Alternative names
Publications (10 of 35) Show all publications
Teruel, M., Coit, P., Dozmorov, M., Cardiel, M., Garcia-De La Torre, I., Maradiaga-Cecena, M. A., . . . Sawalha, A. H. (2017). Genome-Wide DNA Methylation Study in Lupus in an Admixed Mexican Population. Arthritis & Rheumatology, 69(S10), Article ID 178.
Open this publication in new window or tab >>Genome-Wide DNA Methylation Study in Lupus in an Admixed Mexican Population
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2017 (English)In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69, no S10, article id 178Article in journal, Meeting abstract (Other academic) Published
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-346801 (URN)000411824100178 ()
Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2018-03-22Bibliographically approved
Orrú, V., Tsai, S. J., Rueda, B., Fiorillo, E., Stanford, S. M., Dasgupta, J., . . . Bottini, N. (2009). A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus. Human Molecular Genetics, 18(3), 569-579
Open this publication in new window or tab >>A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus
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2009 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 18, no 3, p. 569-579Article in journal (Refereed) Published
Abstract [en]

A gain-of-function R620W polymorphism in the PTPN22 gene, encoding the lymphoid tyrosine phosphatase LYP, has recently emerged as an important risk factor for human autoimmunity. Here we report that another missense substitution (R263Q) within the catalytic domain of LYP leads to reduced phosphatase activity. High-resolution structural analysis revealed the molecular basis for this loss of function. Furthermore, the Q263 variant conferred protection against human systemic lupus erythematosus, reinforcing the proposal that inhibition of LYP activity could be beneficial in human autoimmunity.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-102305 (URN)10.1093/hmg/ddn363 (DOI)000262519300016 ()18981062 (PubMedID)
Available from: 2009-05-06 Created: 2009-05-06 Last updated: 2017-12-13Bibliographically approved
Webb, R., Merrill, J. T., Kelly, J. A., Sestak, A., Kaufman, K. M., Langefeld, C. D., . . . Sawalha, A. H. (2009). A polymorphism within IL21R confers risk for systemic lupus erythematosus. Arthritis and Rheumatism, 60(8), 2402-2407
Open this publication in new window or tab >>A polymorphism within IL21R confers risk for systemic lupus erythematosus
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2009 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, no 8, p. 2402-2407Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Interleukin-21 (IL-21) is a member of the type I cytokine superfamily that has a variety of effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. The expression of IL-21 receptor (IL-21R) is reduced in the B cells of patients with systemic lupus erythematosus (SLE), while serum IL-21 levels are increased both in lupus patients and in some murine lupus models. We recently reported that polymorphisms within the IL21 gene are associated with increased susceptibility to SLE. The aim of this study was to examine the genetic association between single-nucleotide polymorphisms (SNPs) within IL21R and SLE. METHODS: We genotyped 17 SNPs in the IL21R gene in 2 large cohorts of lupus patients (a European-derived cohort and a Hispanic cohort) and in ethnically matched healthy controls. RESULTS: We identified and confirmed the association between rs3093301 within the IL21R gene and SLE in the 2 cohorts (meta-analysis odds ratio 1.16 [95% confidence interval 1.08-1.25], P=1.0x10(-4)). CONCLUSION: Our findings indicate that IL21R is a novel susceptibility gene for SLE.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-122921 (URN)10.1002/art.24658 (DOI)000268973600022 ()19644854 (PubMedID)
Available from: 2010-04-21 Created: 2010-04-21 Last updated: 2017-12-12Bibliographically approved
Kosoy, R., Nassir, R., Tian, C., White, P. A., Butler, L. M., Silva, G., . . . Seldin, M. F. (2009). Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America. Human Mutation, 30(1), 69-78
Open this publication in new window or tab >>Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America
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2009 (English)In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 30, no 1, p. 69-78Article in journal (Refereed) Published
Abstract [en]

To provide a resource for assessing continental ancestry in a wide variety of genetic studies, we identified, validated, and characterized a set of 128 ancestry informative markers (AIMs). The markers were chosen for informativeness, genome-wide distribution, and genotype reproducibility on two platforms (TaqMan assays and Illumina arrays). We analyzed genotyping data from 825 subjects with diverse ancestry, including European, East Asian, Amerindian, African, South Asian, Mexican, and Puerto Rican. A comprehensive set of 128 AIMs and subsets as small as 24 AIMs are shown to be useful tools for ascertaining the origin of subjects from particular continents, and to correct for population stratification in admixed population sample sets. Our findings provide general guidelines for the application of specific AIM subsets as a resource for wide application. We conclude that investigators can use TaqMan assays for the selected AIMs as a simple and cost efficient tool to control for differences in continental ancestry when conducting association studies in ethnically diverse populations.

Keywords
population structure. continental ancestry, population stratification, ancestry informative markers
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-102847 (URN)10.1002/humu.20822 (DOI)000263096300010 ()18683858 (PubMedID)
Available from: 2009-05-12 Created: 2009-05-12 Last updated: 2017-12-13Bibliographically approved
Yu, X., Wieczorek, S., Franke, A., Yin, H., Pierer, M., Sina, C., . . . Ibrahim, S. M. (2009). Association of UCP2 - 866 G/A polymorphism with chronic inflammatory diseases. Genes and Immunity, 10(6), 601-605
Open this publication in new window or tab >>Association of UCP2 - 866 G/A polymorphism with chronic inflammatory diseases
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2009 (English)In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 10, no 6, p. 601-605Article in journal (Refereed) Published
Abstract [en]

We reported earlier that two mitochondrial gene polymorphisms, UCP2 -866 G/A (rs659366) and mtDNA nt13708 G/A (rs28359178), are associated with multiple sclerosis (MS). Here we aim to investigate whether these functional polymorphisms contribute to other eight chronic inflammatory diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Wegener' granulomatosis (WG), Churg-Strauss syndrome (CSS), Crohn's disease (CD), ulcerative colitis (UC), primary sclerosing cholangitis (PSC) and psoriasis. Compared with individual control panels, the UCP2 -866 G/A polymorphism was associated with RA and SLE, and the mtDNA nt13708 G/A polymorphism with RA. Compared with combined controls, the UCP2 -866 G/A polymorphism was associated with SLE, WG, CD and UC. When all eight disease panels and the original MS panel were combined in a meta-analysis, the UCP2 was associated with chronic inflammatory diseases in terms of either alleles (odds ratio (OR)=0.91, 95% confidence interval (95% CI): 0.86-0.96), P=0.0003) or genotypes (OR=0.88, (95% CI: 0.82-0.95), P=0.0008), with the -866A allele associated with a decreased risk to diseases. As the -866A allele increases gene expression, our findings suggest a protective role of the UCP2 protein in chronic inflammatory diseases.

Keywords
mitochondria, chronic inflammatory diseases, uncoupling protein 2
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-111978 (URN)10.1038/gene.2009.29 (DOI)000269493400008 ()19387457 (PubMedID)
Available from: 2010-01-08 Created: 2010-01-05 Last updated: 2018-05-23Bibliographically approved
Douglas, K. B., Windels, D. C., Zhao, J., Gadeliya, A. V., Wu, H., Kaufman, K. M., . . . Boackle, S. A. (2009). Complement receptor 2 polymorphisms associated with systemic lupus erythematosus modulate alternative splicing. Genes and Immunity, 10(5), 457-469
Open this publication in new window or tab >>Complement receptor 2 polymorphisms associated with systemic lupus erythematosus modulate alternative splicing
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2009 (English)In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 10, no 5, p. 457-469Article in journal (Refereed) Published
Abstract [en]

Genetic factors influence susceptibility to systemic lupus erythematosus (SLE). A recent family-based analysis in Caucasian and Chinese populations provided evidence for association of single-nucleotide polymorphisms (SNPs) in the complement receptor 2 (CR2/CD21) gene with SLE. Here we confirmed this result in a case-control analysis of an independent European-derived population including 2084 patients with SLE and 2853 healthy controls. A haplotype formed by the minor alleles of three CR2 SNPs (rs1048971, rs17615, rs4308977) showed significant association with decreased risk of SLE (30.4% in cases vs 32.6% in controls, P=0.016, OR=0.90 (0.82-0.98)). Two of these SNPs are in exon 10, directly 5' of an alternatively spliced exon preferentially expressed in follicular dendritic cells (FDC), and the third is in the alternatively spliced exon. Effects of these SNPs and a fourth SNP in exon 11 (rs17616) on alternative splicing were evaluated. We found that the minor alleles of these SNPs decreased splicing efficiency of exon 11 both in vitro and ex vivo. These findings further implicate CR2 in the pathogenesis of SLE and suggest that CR2 variants alter the maintenance of tolerance and autoantibody production in the secondary lymphoid tissues where B cells and FDCs interact.

Keywords
alternative splicing, systemic lupus erythematosus, complement receptors, single-nucleotide polymorphisms, B cells, follicular dendritic cells
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-122926 (URN)10.1038/gene.2009.27 (DOI)000268168800010 ()19387458 (PubMedID)
Available from: 2010-04-21 Created: 2010-04-21 Last updated: 2017-12-12Bibliographically approved
Meroni, P. L., Tincani, A., Alarcón-Riquelme, M. E., Shoenfeld, Y. & Borghi, M. O. (2009). European Forum on Antiphospholipid Antibodies: research in progress. Lupus, 18(10), 924-929
Open this publication in new window or tab >>European Forum on Antiphospholipid Antibodies: research in progress
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2009 (English)In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 18, no 10, p. 924-929Article in journal (Refereed) Published
Abstract [en]

The research projects of the European Forum on Antiphospholipid Antibodies are representative of how dynamic is this area of investigation. The present review is focused on the most recent projects of the Forum on the aetiopathogenic aspects of the antiphospholipid syndrome (APS). Studies on the genetic background of the APS are ongoing in order to better define the proximity between APS and full-blown systemic lupus erythematosus. However, the analysis of the polymorphisms of genes coding for inflammatory mediators may offer new information on the role of inflammatory processes in triggering thrombotic events as well as the whole susceptibility for developing the vascular manifestations. A systematic and wide detection of serological markers of infectious processes will give new insight on the role of infectious agents in favouring autoimmunity in APS. Owing to the well-known role of vitamin D(3) defect in autoimmune disease, the detection of vitamin plasma levels in APS patients will offer the rationale for a possible therapeutic supplementation. Additional projects are aimed to better characterize the diagnostic/prognostic value of antiphospholipid antibodies (aPL) by defining their epitope specificity and binding avidity. Pregnancy complications represent the obstetric side of APS. Research projects are focussed on the role of complement activation in placenta damage and on the potential ability of aPL to affect the fertility. Finally, a study has been planned in order to draw definitive conclusions on the associations between aPL and atherosclerosis.

Keywords
antiphospholipid antibodies, beta2 glycoprotein I, complement, genetics, inflammation, pregnancy
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-122915 (URN)10.1177/0961203309106916 (DOI)000268841200012 ()19671794 (PubMedID)
Available from: 2010-04-21 Created: 2010-04-21 Last updated: 2017-12-12Bibliographically approved
Han, S., Kim-Howard, X., Deshmukh, H., Kamatani, Y., Viswanathan, P., Guthridge, J. M., . . . Nath, S. K. (2009). Evaluation of imputation-based association in and around the integrin-alpha-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE). Human Molecular Genetics, 18(6), 1171-1180
Open this publication in new window or tab >>Evaluation of imputation-based association in and around the integrin-alpha-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE)
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2009 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 18, no 6, p. 1171-1180Article in journal (Refereed) Published
Abstract [en]

We recently identified a novel non-synonymous variant, rs1143679, at exon 3 of the ITGAM gene associated with systemic lupus erythematosus (SLE) susceptibility in European-Americans (EAs) and African-Americans. Using genome-wide association approach, three other studies also independently reported an association between SLE susceptibility and ITGAM or ITGAM-ITGAX region. The primary objectives of this study are to assess whether single or multiple causal variants from the same gene or any nearby gene(s) are involved in SLE susceptibility and to confirm a robust ITGAM association across nine independent data sets (n = 8211). First, we confirmed our previously reported association of rs1143679 (risk allele 'A') with SLE in EAs (P = 1.0 x 10(-8)) and Hispanic-Americans (P = 2.9 x 10(-5)). Secondly, using a comprehensive imputation-based association test, we found that ITGAM is one of the major non-human leukocyte antigen susceptibility genes for SLE, and the strongest association for EA is the same coding variant rs1143679 (log(10)Bayes factor=20, P = 6.17 x 10(-24)). Thirdly, we determined the robustness of rs1143679 association with SLE across three additional case-control samples, including UK (P = 6.2 x 10(-8)), Colombian (P = 3.6 x 10(-7)), Mexican (P = 0.002), as well as two independent sets of trios from UK (P(TDT) = 1.4 x 10(-5)) and Mexico (P(TDT) = 0.015). A meta-analysis combing all independent data sets greatly reinforces the association (P(meta) = 7.1 x 10(-50), odds ratio = 1.83, 95% confidence interval = 1.69-1.98, n = 10 046). However, this ITGAM association was not observed in the Korean or Japanese samples, in which rs1143679 is monomorphic for the non-risk allele (G). Taken together along with our earlier findings, these results demonstrate that the coding variant, rs1143679, best explains the ITGAM-SLE association, especially in European- and African-derived populations, but not in Asian populations.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-102837 (URN)10.1093/hmg/ddp007 (DOI)000263828100018 ()19129174 (PubMedID)
Available from: 2009-05-12 Created: 2009-05-12 Last updated: 2017-12-13Bibliographically approved
Lu, R., Vidal, G. S., Kelly, J. A., Delgado-Vega, A. M., Howard, X. K., Macwana, S. R., . . . Guthridge, J. M. (2009). Genetic associations of LYN with systemic lupus erythematosus. Genes and Immunity, 10(5), 397-403
Open this publication in new window or tab >>Genetic associations of LYN with systemic lupus erythematosus
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2009 (English)In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 10, no 5, p. 397-403Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
systemic lupus erythematosus, association, LYN, SNP
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-122923 (URN)10.1038/gene.2009.19 (DOI)000268168800004 ()19369946 (PubMedID)
Available from: 2010-04-21 Created: 2010-04-21 Last updated: 2017-12-12Bibliographically approved
Namjou, B., Sestak, A. L., Armstrong, D. L., Zidovetzki, R., Kelly, J. A., Jacob, N., . . . Jacob, C. O. (2009). High-density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups. Arthritis and Rheumatism, 60(4), 1085-1095
Open this publication in new window or tab >>High-density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups
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2009 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, no 4, p. 1085-1095Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder, with complex etiology and a strong genetic component. Recently, gene products involved in the interferon pathway have been under intense investigation in terms of the pathogenesis of SLE. STAT-1 and STAT-4 are transcription factors that play key roles in the interferon and Th1 signaling pathways, making them attractive candidates for involvement in SLE susceptibility. METHODS: Fifty-six single-nucleotide polymorphisms (SNPs) across STAT1 and STAT4 on chromosome 2 were genotyped using the Illumina platform, as part of an extensive association study in a large collection of 9,923 lupus patients and control subjects from different racial groups. DNA samples were obtained from the peripheral blood of patients with SLE and control subjects. Principal components analyses and population-based case-control association analyses were performed, and the P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated. RESULTS: We observed strong genetic associations with SLE and multiple SNPs located within STAT4 in different ethnic groups (Fisher's combined P = 7.02 x 10(-25)). In addition to strongly confirming the previously reported association in the third intronic region of this gene, we identified additional haplotypic association across STAT4 and, in particular, a common risk haplotype that is found in multiple racial groups. In contrast, only a relatively weak suggestive association was observed with STAT1, probably due to its proximity to STAT4. CONCLUSION: Our findings indicate that STAT4 is likely to be a crucial component in SLE pathogenesis in multiple racial groups. Knowledge of the functional effects of this association, when they are revealed, might improve our understanding of the disease and provide new therapeutic targets.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-102308 (URN)10.1002/art.24387 (DOI)000265152800022 ()19333953 (PubMedID)
Available from: 2009-05-06 Created: 2009-05-06 Last updated: 2017-12-13Bibliographically approved
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