Association of MASP-2 levels and MASP2 gene polymorphisms with rheumatoid arthritis in patients and their relatives.

<h4>Background</h4>Mannan-binding lectin-associated serine protease 2 (MASP-2) is a key protein of the lectin pathway of complement. MASP-2 levels have been associated with different polymorphisms within MASP2 gene as well as with the risk for inflammatory disorders and infections. Despi...

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Autores principales:	Isabela Goeldner, Thelma Skare, Angelica B W Boldt, Flavia R Nass, Iara J Messias-Reason, Shirley R Utiyama
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1d5a3c09250d4b238d3fa5d93d0e5749
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spelling	oai:doaj.org-article:1d5a3c09250d4b238d3fa5d93d0e57492021-11-18T08:28:08ZAssociation of MASP-2 levels and MASP2 gene polymorphisms with rheumatoid arthritis in patients and their relatives.1932-620310.1371/journal.pone.0090979https://doaj.org/article/1d5a3c09250d4b238d3fa5d93d0e57492014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24632598/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Mannan-binding lectin-associated serine protease 2 (MASP-2) is a key protein of the lectin pathway of complement. MASP-2 levels have been associated with different polymorphisms within MASP2 gene as well as with the risk for inflammatory disorders and infections. Despite its clinical importance, MASP-2 remains poorly investigated in rheumatoid arthritis (RA).<h4>Methods</h4>In this case-control study, we measured MASP-2 serum levels in 156 RA patients, 44 patient relatives, and 100 controls from Southern Brazil, associating the results with nine MASP2 polymorphisms in all patients, 111 relatives, and 230 controls genotyped with multiplex SSP-PCR.<h4>Results</h4>MASP-2 levels were lower in patients than in controls and relatives (medians 181 vs. 340 or 285 ng/ml, respectively, P<0.0001). Conversely, high MASP-2 levels were associated with lower susceptibility to RA and to articular symptoms independently of age, gender, ethnicity, smoking habit, anti-CCP and rheumatoid factor positivity (OR = 0.05 [95%CI = 0.019-0.13], P<0.0001 between patients and controls; OR = 0.12, [95%CI = 0.03-0.45], P = 0.002 between patients and relatives; OR = 0.06, [95%CI = 0.004-0.73], P = 0.03 between relatives with and without articular symptoms). MASP2 haplotypes 2A1 and 2B1-i were associated with increased susceptibility to RA (OR = 3.32 [95%CI = 1.48-7.45], P = 0.004). Deficiency-causing p.120G and p.439H substitutions were associated with five times increased susceptibility to articular symptoms in relatives (OR = 5.13 [95%CI = 1.36-20.84], P = 0.02). There was no association of MASP-2 levels or MASP2 polymorphisms with autoantibodies, Sjögren's syndrome, nodules and functional class.<h4>Conclusions</h4>In this study, we found the first evidence that MASP-2 deficiency might play an important role in the development of RA and articular symptoms among relatives of RA patients.Isabela GoeldnerThelma SkareAngelica B W BoldtFlavia R NassIara J Messias-ReasonShirley R UtiyamaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e90979 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Isabela Goeldner Thelma Skare Angelica B W Boldt Flavia R Nass Iara J Messias-Reason Shirley R Utiyama Association of MASP-2 levels and MASP2 gene polymorphisms with rheumatoid arthritis in patients and their relatives.
description	<h4>Background</h4>Mannan-binding lectin-associated serine protease 2 (MASP-2) is a key protein of the lectin pathway of complement. MASP-2 levels have been associated with different polymorphisms within MASP2 gene as well as with the risk for inflammatory disorders and infections. Despite its clinical importance, MASP-2 remains poorly investigated in rheumatoid arthritis (RA).<h4>Methods</h4>In this case-control study, we measured MASP-2 serum levels in 156 RA patients, 44 patient relatives, and 100 controls from Southern Brazil, associating the results with nine MASP2 polymorphisms in all patients, 111 relatives, and 230 controls genotyped with multiplex SSP-PCR.<h4>Results</h4>MASP-2 levels were lower in patients than in controls and relatives (medians 181 vs. 340 or 285 ng/ml, respectively, P<0.0001). Conversely, high MASP-2 levels were associated with lower susceptibility to RA and to articular symptoms independently of age, gender, ethnicity, smoking habit, anti-CCP and rheumatoid factor positivity (OR = 0.05 [95%CI = 0.019-0.13], P<0.0001 between patients and controls; OR = 0.12, [95%CI = 0.03-0.45], P = 0.002 between patients and relatives; OR = 0.06, [95%CI = 0.004-0.73], P = 0.03 between relatives with and without articular symptoms). MASP2 haplotypes 2A1 and 2B1-i were associated with increased susceptibility to RA (OR = 3.32 [95%CI = 1.48-7.45], P = 0.004). Deficiency-causing p.120G and p.439H substitutions were associated with five times increased susceptibility to articular symptoms in relatives (OR = 5.13 [95%CI = 1.36-20.84], P = 0.02). There was no association of MASP-2 levels or MASP2 polymorphisms with autoantibodies, Sjögren's syndrome, nodules and functional class.<h4>Conclusions</h4>In this study, we found the first evidence that MASP-2 deficiency might play an important role in the development of RA and articular symptoms among relatives of RA patients.
format	article
author	Isabela Goeldner Thelma Skare Angelica B W Boldt Flavia R Nass Iara J Messias-Reason Shirley R Utiyama
author_facet	Isabela Goeldner Thelma Skare Angelica B W Boldt Flavia R Nass Iara J Messias-Reason Shirley R Utiyama
author_sort	Isabela Goeldner
title	Association of MASP-2 levels and MASP2 gene polymorphisms with rheumatoid arthritis in patients and their relatives.
title_short	Association of MASP-2 levels and MASP2 gene polymorphisms with rheumatoid arthritis in patients and their relatives.
title_full	Association of MASP-2 levels and MASP2 gene polymorphisms with rheumatoid arthritis in patients and their relatives.
title_fullStr	Association of MASP-2 levels and MASP2 gene polymorphisms with rheumatoid arthritis in patients and their relatives.
title_full_unstemmed	Association of MASP-2 levels and MASP2 gene polymorphisms with rheumatoid arthritis in patients and their relatives.
title_sort	association of masp-2 levels and masp2 gene polymorphisms with rheumatoid arthritis in patients and their relatives.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/1d5a3c09250d4b238d3fa5d93d0e5749
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Association of MASP-2 levels and MASP2 gene polymorphisms with rheumatoid arthritis in patients and their relatives.

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