Sökning: onr:"swepub:oai:DiVA.org:uu-102307" >
Variants within MEC...
Variants within MECP2, a key transcription regulator, are associated with increased susceptibility to lupus and differential gene expression in patients with systemic lupus erythematosus
-
Webb, Ryan (författare)
-
Wren, Jonathan D. (författare)
-
Jeffries, Matlock (författare)
-
visa fler...
-
Kelly, Jennifer A. (författare)
-
Kaufman, Kenneth M. (författare)
-
Tang, Yuhong (författare)
-
Frank, Mark Barton (författare)
-
Merrill, Joan (författare)
-
Kimberly, Robert P. (författare)
-
Edberg, Jeffrey C. (författare)
-
Ramsey-Goldman, Rosalind (författare)
-
Petri, Michelle (författare)
-
Reveille, John D. (författare)
-
Alarcón, Graciela S. (författare)
-
Vilá, Luis M. (författare)
-
- Alarcón-Riquelme, Marta E. (författare)
- Uppsala universitet,Institutionen för genetik och patologi
-
James, Judith A. (författare)
-
Vyse, Timothy J. (författare)
-
Moser, Kathy L. (författare)
-
Gaffney, Patrick M. (författare)
-
Gilkeson, Gary S. (författare)
-
Harley, John B. (författare)
-
Sawalha, Amr H. (författare)
-
visa färre...
-
(creator_code:org_t)
- Wiley, 2009
- 2009
- Engelska.
-
Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:4, s. 1076-1084
- Relaterad länk:
-
https://onlinelibrar...
-
visa fler...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- OBJECTIVE: Both genetic and epigenetic factors play an important role in the pathogenesis of lupus. The aim of this study was to examine methyl-CpG-binding protein 2 gene (MECP2) polymorphisms in a large cohort of patients with lupus and control subjects, and to determine the functional consequences of the lupus-associated MECP2 haplotype. METHODS: We genotyped 18 single-nucleotide polymorphisms within MECP2, located on chromosome Xq28, in a large cohort of patients with lupus and control subjects of European descent. We studied the functional effects of the lupus-associated MECP2 haplotype by determining gene expression profiles in B cell lines in female lupus patients with and those without the lupus-associated MECP2 risk haplotype. RESULTS: We confirmed, replicated, and extended the genetic association between lupus and genetic markers within MECP2 in a large independent cohort of lupus patients and control subjects of European descent (odds ratio 1.35, P = 6.65 x 10(-11)). MECP2 is a dichotomous transcription regulator that either activates or represses gene expression. We identified 128 genes that are differentially expressed in lupus patients with the disease-associated MECP2 haplotype; most ( approximately 81%) were up-regulated. Genes that were up-regulated had significantly more CpG islands in their promoter regions compared with genes that were down-regulated. Gene ontology analysis using the differentially expressed genes revealed significant association with epigenetic regulatory mechanisms, suggesting that these genes are targets for MECP2 regulation in B cells. Furthermore, at least 13 of the 104 up-regulated genes are regulated by interferon. The disease-risk MECP2 haplotype was associated with increased expression of the MECP2 transcription coactivator CREB1 and decreased expression of the corepressor histone deacetylase 1. CONCLUSION: Polymorphism in the MECP2 locus is associated with lupus and, at least in part, contributes to the interferon signature observed in lupus patients.
Nyckelord
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Webb, Ryan
-
Wren, Jonathan D ...
-
Jeffries, Matloc ...
-
Kelly, Jennifer ...
-
Kaufman, Kenneth ...
-
Tang, Yuhong
-
visa fler...
-
Frank, Mark Bart ...
-
Merrill, Joan
-
Kimberly, Robert ...
-
Edberg, Jeffrey ...
-
Ramsey-Goldman, ...
-
Petri, Michelle
-
Reveille, John D ...
-
Alarcón, Graciel ...
-
Vilá, Luis M.
-
Alarcón-Riquelme ...
-
James, Judith A.
-
Vyse, Timothy J.
-
Moser, Kathy L.
-
Gaffney, Patrick ...
-
Gilkeson, Gary S ...
-
Harley, John B.
-
Sawalha, Amr H.
-
visa färre...
- Artiklar i publikationen
-
Arthritis and Rh ...
- Av lärosätet
-
Uppsala universitet