Sequencing of the ST2 Gene Reveals a Haplotype That Determines Serum Total ST2 Levels in Individuals of African Ancestry

Detalhes bibliográficos
Autor(a) principal: Huang, Lili
Data de Publicação: 2013
Outros Autores: Gao, Li, Figueiredo, Camila, Rafaels, Nicholas M., Vergara, Candelaria I., Ruczinski, Ingo, Beaty, Terri H., Barnes, Kathleen C., Mathias, Rasika A.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFBA
Texto Completo: http://www.repositorio.ufba.br/ri/handle/ri/12073
Resumo: Texto completo. Acesso restrito. p. 53
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spelling Huang, LiliGao, LiFigueiredo, CamilaRafaels, Nicholas M.Vergara, Candelaria I.Ruczinski, IngoBeaty, Terri H.Barnes, Kathleen C.Mathias, Rasika A.Huang, LiliGao, LiFigueiredo, CamilaRafaels, Nicholas M.Vergara, Candelaria I.Ruczinski, IngoBeaty, Terri H.Barnes, Kathleen C.Mathias, Rasika A.2013-07-03T16:50:09Z2013-07-03T16:50:09Z20130091-6749http://www.repositorio.ufba.br/ri/handle/ri/12073v. 131, n. 2Texto completo. Acesso restrito. p. 53Rationale ST2 (IL1RL1), is an IL1 family receptor that mediates important effectors of Th2 functions. Its soluble form (sST2) neutralizes its ligand, IL-33, by acting as a decoy receptor. Serum sST2 has been used as a biomarker for disease severity and outcome for multiple inflammatory and lung diseases, including atopic asthma. We undertook a targeted deep resequencing of ST2 gene in 241 samples of African ancestry to identify ST2variants controlling serum sST2 levels. Methods Serum sST2 concentration was measured by ELISA, and resequencing of ∼50kb (chr2:102922962-102973497) encompassing the ST2gene was performed using Illumina's HiSeq2000. Single-variant tests for all common variants (MAF≥5%) were performed using linear regression assuming an additive model on log serum total ST2 considering age, gender and the first two principal components on a pre-existing genome-wide association panel of ancestry informative markers to adjust for admixture. Results A total of 565 ST2 variants were identified, 192 of which had a MAF≥5% including 3 coding synonymous and 6 missense variants. In the sST2 level analysis, ten SNPs in strong linkage disequilibrium yielded p-value less than 10-3; a single common haplotype (frequency=65%) across all 10 SNPs yielded an overall p-value = 0.0002 and was negatively associated with sST2 levels (β = -0.09). Conclusions Sequencing ST2 gene revealed a novel haplotype influencing sST2 levels in individuals of African ancestry, including 5 variants mapping to intron 1 and 5 mapping to the 5’ region of ST2. Further work is ongoing to fully explore this association in an additional 400 subjects of African ancestry.Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-07-03T16:50:09Z No. of bitstreams: 1 3333333333333.pdf: 44766 bytes, checksum: 9c12787c8508e70b11e35307361711c2 (MD5)Made available in DSpace on 2013-07-03T16:50:09Z (GMT). No. of bitstreams: 1 3333333333333.pdf: 44766 bytes, checksum: 9c12787c8508e70b11e35307361711c2 (MD5) Previous issue date: 2013SalvadorJournal of Allergy and Clinical Immunologyhttp://dx.doi.org/10.1016/j.jaci.2012.12.873reponame:Repositório Institucional da UFBAinstname:Universidade Federal da Bahia (UFBA)instacron:UFBASequencing of the ST2 Gene Reveals a Haplotype That Determines Serum Total ST2 Levels in Individuals of African AncestryJournal of Allergy and Clinical Immunologyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleenginfo:eu-repo/semantics/openAccessORIGINAL3333333333333.pdf3333333333333.pdfapplication/pdf44766https://repositorio.ufba.br/bitstream/ri/12073/1/3333333333333.pdf9c12787c8508e70b11e35307361711c2MD51LICENSElicense.txtlicense.txttext/plain1762https://repositorio.ufba.br/bitstream/ri/12073/2/license.txt1b89a9a0548218172d7c829f87a0eab9MD52TEXT3333333333333.pdf.txt3333333333333.pdf.txtExtracted texttext/plain7169https://repositorio.ufba.br/bitstream/ri/12073/3/3333333333333.pdf.txtf97339910ffc65cca0cf1340b82adf75MD53ri/120732022-07-05 14:02:51.873oai:repositorio.ufba.br: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Repositório InstitucionalPUBhttp://192.188.11.11:8080/oai/requestopendoar:19322022-07-05T17:02:51Repositório Institucional da UFBA - Universidade Federal da Bahia (UFBA)false
dc.title.pt_BR.fl_str_mv Sequencing of the ST2 Gene Reveals a Haplotype That Determines Serum Total ST2 Levels in Individuals of African Ancestry
dc.title.alternative.pt_BR.fl_str_mv Journal of Allergy and Clinical Immunology
title Sequencing of the ST2 Gene Reveals a Haplotype That Determines Serum Total ST2 Levels in Individuals of African Ancestry
spellingShingle Sequencing of the ST2 Gene Reveals a Haplotype That Determines Serum Total ST2 Levels in Individuals of African Ancestry
Huang, Lili
title_short Sequencing of the ST2 Gene Reveals a Haplotype That Determines Serum Total ST2 Levels in Individuals of African Ancestry
title_full Sequencing of the ST2 Gene Reveals a Haplotype That Determines Serum Total ST2 Levels in Individuals of African Ancestry
title_fullStr Sequencing of the ST2 Gene Reveals a Haplotype That Determines Serum Total ST2 Levels in Individuals of African Ancestry
title_full_unstemmed Sequencing of the ST2 Gene Reveals a Haplotype That Determines Serum Total ST2 Levels in Individuals of African Ancestry
title_sort Sequencing of the ST2 Gene Reveals a Haplotype That Determines Serum Total ST2 Levels in Individuals of African Ancestry
author Huang, Lili
author_facet Huang, Lili
Gao, Li
Figueiredo, Camila
Rafaels, Nicholas M.
Vergara, Candelaria I.
Ruczinski, Ingo
Beaty, Terri H.
Barnes, Kathleen C.
Mathias, Rasika A.
author_role author
author2 Gao, Li
Figueiredo, Camila
Rafaels, Nicholas M.
Vergara, Candelaria I.
Ruczinski, Ingo
Beaty, Terri H.
Barnes, Kathleen C.
Mathias, Rasika A.
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Huang, Lili
Gao, Li
Figueiredo, Camila
Rafaels, Nicholas M.
Vergara, Candelaria I.
Ruczinski, Ingo
Beaty, Terri H.
Barnes, Kathleen C.
Mathias, Rasika A.
Huang, Lili
Gao, Li
Figueiredo, Camila
Rafaels, Nicholas M.
Vergara, Candelaria I.
Ruczinski, Ingo
Beaty, Terri H.
Barnes, Kathleen C.
Mathias, Rasika A.
description Texto completo. Acesso restrito. p. 53
publishDate 2013
dc.date.accessioned.fl_str_mv 2013-07-03T16:50:09Z
dc.date.available.fl_str_mv 2013-07-03T16:50:09Z
dc.date.issued.fl_str_mv 2013
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://www.repositorio.ufba.br/ri/handle/ri/12073
dc.identifier.issn.none.fl_str_mv 0091-6749
dc.identifier.number.pt_BR.fl_str_mv v. 131, n. 2
identifier_str_mv 0091-6749
v. 131, n. 2
url http://www.repositorio.ufba.br/ri/handle/ri/12073
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Journal of Allergy and Clinical Immunology
publisher.none.fl_str_mv Journal of Allergy and Clinical Immunology
dc.source.pt_BR.fl_str_mv http://dx.doi.org/10.1016/j.jaci.2012.12.873
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFBA
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