Mannose-binding lectin and Ficolin-2 gene polymorphisms predispose to cytomegalovirus (re)infection after orthotopic liver transplantation

Rooij, Bert-Jan F. de; Beek, Martha T. van der; Hoek, Bart van; Vossen, Ann C.T.M.; Hove, W. Rogier ten; Roos, Anja; Schaapherder, Alexander F.; Porte, Robert J.; Reijden, Johan J. van der; Coenraad, Minneke J.; Hommes, Daniël W.; Verspaget, Hein W.

doi:10.1016/j.jhep.2011.01.039

Cited by 38 publications

(40 citation statements)

References 32 publications

(37 reference statements)

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“…The 258S variant was also found associated by others with earlier onset of Pseudomonas aeruginosa colonization in cystic fibrosis patients [31]. In contrast to our findings, homozygosity for this variant was associated with protection against cutaneous leishmaniasis in Syria [32] and the presence of this allele, with protection against cytomegalovirus, but not bacterial infections, after orthotopic liver transplantation [33], [34]. It was not associated with respiratory tract infections in Dutch children [35], nor with invasive pneumococcal disease [36], rheumatoid arthritis [37] and Behçet’s disease in Japan [38].…”

Section: Discussioncontrasting

confidence: 94%

Association of L-Ficolin Levels and FCN2 Genotypes with Chronic Chagas Disease

et al. 2013

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BackgroundL-ficolin (encoded by FCN2) binds to acetylated sugar moieties of many pathogens, including Trypanosoma cruzi, promoting their phagocytosis and lysis by the complement system.MethodsWe 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).ResultsPatients 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.ConclusionThe 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.

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Section: Discussioncontrasting

confidence: 94%

Association of L-Ficolin Levels and FCN2 Genotypes with Chronic Chagas Disease

et al. 2013

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“…Heterozygosity for SNPs −64 A > C and +6424 G > T was associated with earlier onset of Pseudomonas aeruginosa colonization in cystic fibrosis (Haerynck et al 2012). Moreover, an interplay between liver donor’s and recipient’s FCN2 +6424 genotype may influence the risk of cytomegalovirus infection in the latter (de Rooij et al 2011). Homozygosity for the variant (T) allele seemed to protect from cutaneous leishmaniasis (Assaf et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Cost-effective procedures for genotyping of human FCN2 gene single nucleotide polymorphisms

2013

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L-ficolin (ficolin-2) is a complement-activating pattern-recognition lectin taking part in the innate immune response. Both its serum concentration and sugar binding capacity are influenced by single nucleotide polymorphisms (SNP) of the corresponding FCN2 gene. Cost-effective and simple procedures, based on polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism for an investigation of four FCN2 SNPs are proposed: −64 A > C (rs7865453), −4 A > G (rs17514136; both located in the promoter region), +6359 C > T (rs17549193), +6424 G > T (rs7851696; both in exon 8). Variant alleles of −64 and +6424 (in strong linkage disequlibrium) are known to be associated with low L-ficolin level or activity. In contrast, variant alleles at positions −4 and +6359 (also in strong linkage disequlibrium) correspond to higher values. Since several L-ficolin clinical associations have been reported, FCN2 genotyping seems to be a valuable tool for disease association studies.

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“…Twenty‐one genetic variants in the MBL2, FCN2, MASP2, TLR2, TLR4 and NOD2 genes with known functional implications on protein level were evaluated . Genomic DNA was extracted from 10 mL EDTA peripheral blood samples.…”

Section: Methodsmentioning

confidence: 99%

Genetic variants of innate immunity receptors are associated with mortality in cirrhotic patients with bacterial infection

Schaapman

Amorós

Reijden

et al. 2020

Liver International

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Background & Aims Acute‐on‐chronic liver failure (ACLF) is characterized by acute decompensation of cirrhosis (AD), organ failure(s) and high risk of short‐term mortality with bacterial infection frequently as precipitating event. Innate immune pattern recognition receptors and members of the lectin pathway of complement activation are crucial to the innate immune response to pathogens. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) of innate immune components are associated with the occurrence of bacterial infections or mortality in patients with cirrhosis hospitalized for AD or ACLF. Methods Twenty‐one innate immunity SNPs with known functional implications were genotyped in 826 AD/ACLF patients included in the CANONIC study. Associations between baseline characteristics of the patients, the occurrence of bacterial infections and survival rate at 90 days of follow‐up in relation to the innate immunity genetic variants were analysed. Results The NOD2‐G908R genetic variant was associated with mortality (HR 2.25, P = .004) independently of age and MELD Score. This association was also found in a predefined subgroup analysis in patients with bacterial infections (HR 2.78, P < .001) along with MBL_Yx (HR 1.72, P = .008) and MASP2_371 (HR 1.67, P = .012) genetic variants. None of the analysed SNPs were significantly associated with the occurrence of acute bacterial infections or spontaneous bacterial peritonitis in particular. Conclusions Innate immune system‐specific NOD2‐G908R, MBL_Yx and MASP2_371 genetic variants were independently associated with increased risk of short‐term mortality in AD/ACLF patients with bacterial infection.

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Mannose-binding lectin and Ficolin-2 gene polymorphisms predispose to cytomegalovirus (re)infection after orthotopic liver transplantation

Cited by 38 publications

References 32 publications

Association of L-Ficolin Levels and FCN2 Genotypes with Chronic Chagas Disease

Association of L-Ficolin Levels and FCN2 Genotypes with Chronic Chagas Disease

Cost-effective procedures for genotyping of human FCN2 gene single nucleotide polymorphisms

Genetic variants of innate immunity receptors are associated with mortality in cirrhotic patients with bacterial infection

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