Association of L-ficolin levels and FCN2 genotypes with chronic Chagas disease.

<h4>Background</h4>L-ficolin (encoded by FCN2) binds to acetylated sugar moieties of many pathogens, including Trypanosoma cruzi, promoting their phagocytosis and lysis by the complement system.<h4>Methods</h4>We investigated L-ficolin levels in 160 T. cruzi infected patients...

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Autores principales:	Paola R Luz, Angelica B W Boldt, Caroline Grisbach, Jürgen F J Kun, Thirumalaisamy P Velavan, Iara J T Messias-Reason
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7ba6002344eb4bd6a08b951ffdefa543
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spelling	oai:doaj.org-article:7ba6002344eb4bd6a08b951ffdefa5432021-11-18T07:50:38ZAssociation of L-ficolin levels and FCN2 genotypes with chronic Chagas disease.1932-620310.1371/journal.pone.0060237https://doaj.org/article/7ba6002344eb4bd6a08b951ffdefa5432013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23593180/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>L-ficolin (encoded by FCN2) binds to acetylated sugar moieties of many pathogens, including Trypanosoma cruzi, promoting their phagocytosis and lysis by the complement system.<h4>Methods</h4>We investigated L-ficolin levels in 160 T. cruzi infected patients with chronic Chagas disease and 71 healthy individuals, and FCN2 polymorphisms (-986 G>A, -602 G>A, and -4 A>G in the promoter and A258S in exon 8) in 243 patients, being 88 indeterminate (asymptomatic), 96 with cardiac, 23 with digestive and 33 with cardiodigestive manifestations (two were unspecified) and 305 controls (135 for A258S).<h4>Results</h4>Patients presented lower L-ficolin plasma levels than controls (p<0.0001). Among the different groups of cardiac commitment, individuals with moderate forms had higher L-ficolin levels than the severe forms (P = 0.039). Lower L-ficolin levels were found associated with the 258S variant in the patients (P = 0.034). We found less -4A/G heterozygotes in the cardiac patients, than in the controls (OR = 0.56 [95% CI = 0.33-0.94], P = 0.034). Heterozygote -4A/G genotypes with the 258S variant and 258SS homozygotes were nevertheless more frequent among cardiodigestive patients than in controls (OR = 14.1 [95% CI = 3.5-56.8], P = 0.0001) and in indeterminate patients (OR = 3.2 [95% CI = 1.1-9.4], P = 0.037). We also found an association of the allelic frequency of the 258S variant with cardiodigestive Chagas disease compared to controls (OR = 2.24 [95% CI = 1.1-4.5], P = 0.037). Thus, decreased patient levels of L-ficolin reflect not only protein consumption due to the disease process, but also the higher frequency of the 258S variant in patients with cardiodigestive symptoms.<h4>Conclusion</h4>The very first study on Brazilian cohort associates both L-ficolin plasma levels and FCN2 variants to Chagas disease and subsequent disease progression. The prognostic value of L-ficolin levels and the FCN2*A258S polymorphism should be further evaluated in other settings.Paola R LuzAngelica B W BoldtCaroline GrisbachJürgen F J KunThirumalaisamy P VelavanIara J T Messias-ReasonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e60237 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paola R Luz Angelica B W Boldt Caroline Grisbach Jürgen F J Kun Thirumalaisamy P Velavan Iara J T Messias-Reason Association of L-ficolin levels and FCN2 genotypes with chronic Chagas disease.
description	<h4>Background</h4>L-ficolin (encoded by FCN2) binds to acetylated sugar moieties of many pathogens, including Trypanosoma cruzi, promoting their phagocytosis and lysis by the complement system.<h4>Methods</h4>We investigated L-ficolin levels in 160 T. cruzi infected patients with chronic Chagas disease and 71 healthy individuals, and FCN2 polymorphisms (-986 G>A, -602 G>A, and -4 A>G in the promoter and A258S in exon 8) in 243 patients, being 88 indeterminate (asymptomatic), 96 with cardiac, 23 with digestive and 33 with cardiodigestive manifestations (two were unspecified) and 305 controls (135 for A258S).<h4>Results</h4>Patients presented lower L-ficolin plasma levels than controls (p<0.0001). Among the different groups of cardiac commitment, individuals with moderate forms had higher L-ficolin levels than the severe forms (P = 0.039). Lower L-ficolin levels were found associated with the 258S variant in the patients (P = 0.034). We found less -4A/G heterozygotes in the cardiac patients, than in the controls (OR = 0.56 [95% CI = 0.33-0.94], P = 0.034). Heterozygote -4A/G genotypes with the 258S variant and 258SS homozygotes were nevertheless more frequent among cardiodigestive patients than in controls (OR = 14.1 [95% CI = 3.5-56.8], P = 0.0001) and in indeterminate patients (OR = 3.2 [95% CI = 1.1-9.4], P = 0.037). We also found an association of the allelic frequency of the 258S variant with cardiodigestive Chagas disease compared to controls (OR = 2.24 [95% CI = 1.1-4.5], P = 0.037). Thus, decreased patient levels of L-ficolin reflect not only protein consumption due to the disease process, but also the higher frequency of the 258S variant in patients with cardiodigestive symptoms.<h4>Conclusion</h4>The very first study on Brazilian cohort associates both L-ficolin plasma levels and FCN2 variants to Chagas disease and subsequent disease progression. The prognostic value of L-ficolin levels and the FCN2*A258S polymorphism should be further evaluated in other settings.
format	article
author	Paola R Luz Angelica B W Boldt Caroline Grisbach Jürgen F J Kun Thirumalaisamy P Velavan Iara J T Messias-Reason
author_facet	Paola R Luz Angelica B W Boldt Caroline Grisbach Jürgen F J Kun Thirumalaisamy P Velavan Iara J T Messias-Reason
author_sort	Paola R Luz
title	Association of L-ficolin levels and FCN2 genotypes with chronic Chagas disease.
title_short	Association of L-ficolin levels and FCN2 genotypes with chronic Chagas disease.
title_full	Association of L-ficolin levels and FCN2 genotypes with chronic Chagas disease.
title_fullStr	Association of L-ficolin levels and FCN2 genotypes with chronic Chagas disease.
title_full_unstemmed	Association of L-ficolin levels and FCN2 genotypes with chronic Chagas disease.
title_sort	association of l-ficolin levels and fcn2 genotypes with chronic chagas disease.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/7ba6002344eb4bd6a08b951ffdefa543
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Association of L-ficolin levels and FCN2 genotypes with chronic Chagas disease.

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