Frequency and distribution of FCN2 and FCN3 functional variants among MBL2 genotypes

Bjarnadóttir, Helga; Arnardottir, Margret; Lúðvíksson, Björn Rúnar

doi:10.1007/s00251-016-0903-4

Cited by 14 publications

(32 citation statements)

References 88 publications

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“…For instance, when the level of MBL is low, the level of L-ficolin, H-ficolin or both was high, and this may be due to the necessity of compensation within the lectin pathway. It has been reported that when MBL deficient the level of L-ficolin increased [40] due to the genetic balance and importance of the reparation in the immune system [41].…”

Section: Discussionmentioning

confidence: 99%

Novel Polymorphism in a Promoter of MBL2 Gene Result in Lower MBL Expression in Chronic Infection Caused by HCV

Jalal¹

2020

KJAR

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The Pathogen Recognition Receptors (PRRs) is an active protein in the immune system. The PRRs that secreted in the liver and we addressed were L-ficolin, MBL and H-ficolin. Previous studies revealed that both MBL and L-ficolin were hampered the HCV entry and infectivity. However, H-ficolin impact still needs to be addressed more so as determining their role during HCV infection. For these purposes, we aimed to determine the effect of different level in the serum of these proteins on the HCV infection and treatment outcome. Initially, we selected (25) HCV positive patients and (25) HCV negative control patients from the Trent Cohort and Regional Haemophiliac Study and to present the differences in serum concentrations of MBL, H- and L-ficolin. The level of these proteins was measured by ELISA method and compared with each other based on the detected SNPs by PCR and sequencing methods in the responsible genes. Our results showed that the polymorphism at position -221 in the MBL2 promoter significantly reduce the level of MBL protein more than the SNP at position -551. Interestingly, a new deletion of six nucleotides [AGGAAG] detected in the promoter at position -319 to -324 that succeeded by four other mutations at position -328, -336, -349 and -427 in most of the analyzed sequences. The 6bp deletion was statistically decreasing the concentration of MBL below 1µg.mL-1, precisely among non-responder patients. In conclusion, the existence of the new deletion in the promoter region of MBL2 gene and the additional newly detected polymorphisms, reduce the level of MBL protein and as a result impacts on the response to treatment among HCV-infected patients.

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Section: Discussionmentioning

confidence: 99%

Novel Polymorphism in a Promoter of MBL2 Gene Result in Lower MBL Expression in Chronic Infection Caused by HCV

Jalal¹

2020

KJAR

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“…Due to its rarity, it is still unclear whether it is a lifethreatening condition with variable penetrance or acts as a disease modifier [89]. Partial ficolin-2 (or L-ficolin) and ficolin-3 (or H-ficolin) insufficiencies are not well studied and are of uncertain clinical significance [90,91].…”

Section: Lectinmentioning

confidence: 99%

“…Malpuech, Michels and Mingarelli-Carnevale (3MC) syndrome is characterized by facial dysmorphia and other developmental defects such as cleft lip and palate, postnatal growth deficiency, cognitive impairment and hearing loss [13,90,91,103]. It is caused by homozygous mutations in the MASP1 gene (3MC syndrome 1) or members of the collectin subfamily COLEC10 or COLEC11 (3MC syndrome 2) [103].…”

Section: Masp1mentioning

confidence: 99%

European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) Complement Guideline: Deficiencies, Diagnosis, and Management

Brodszki

Frazer‐Abel

Grumach³

et al. 2020

J Clin Immunol

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This guideline aims to describe the complement system and the functions of the constituent pathways, with particular focus on primary immunodeficiencies (PIDs) and their diagnosis and management. The complement system is a crucial part of the innate immune system, with multiple membrane-bound and soluble components. There are three distinct enzymatic cascade pathways within the complement system, the classical, alternative and lectin pathways, which converge with the cleavage of central C3. Complement deficiencies account for ~5% of PIDs. The clinical consequences of inherited defects in the complement system are protean and include increased susceptibility to infection, autoimmune diseases (e.g., systemic lupus erythematosus), age-related macular degeneration, renal disorders (e.g., atypical hemolytic uremic syndrome) and angioedema. Modern complement analysis allows an in-depth insight into the functional and molecular basis of nearly all complement deficiencies. However, therapeutic options remain relatively limited for the majority of complement deficiencies with the exception of hereditary angioedema and inhibition of an overactivated complement system in regulation defects. Current management strategies for complement disorders associated with infection include education, family testing, vaccinations, antibiotics and emergency planning.

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“…Homozygosity for +1637delC happens very rarely (1-2 %): only 6 cases have been described in the literature available (all of them suffered from severe infections in early childhood). Data on the population frequency of heterozygous carriage are also scarce, i. e. 15 heterozygotes out of 483 examined individuals were identified in the Icelandic cohort of healthy donors (the frequency was 1.5 %) (Bjarnadottir et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Prevalence of the polymorphic H-ficolin (FCN3) genes and mannosebinding lectin-associated serine protease-2 (MASP2) in indigenous populations from the Russian Arctic regions

Смольникова

Tereshchenko

2022

Vestn. VOGiS

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Lectins, being the main proteins of the lectin pathway activating the complement system, are encoded by polymorphic genes, wherein point mutations cause the protein conformation and expression to change, which turns out to have an effect on the functionality and ability to respond to the pathogen. In the current study, largescale data on the population genotype distribution of the genes for H-ficolin FCN3 rs28357092 and mannose-binding lectin-associated serine protease MASP2 rs72550870 among the indigenous peoples of the Russian Arctic regions (Nenets, Dolgans and Nganasans, a mixed population and Russians: a total sample was about 1000 newborns) have been obtained for the first time. Genotyping was carried out using RT-PCR. The frequency of the homozygous variant del/del FCN3 rs28357092 associated with the total absence of the most powerful activator of the lectin complement pathway, N-ficolin, was revealed; 0 % in the Nenets, 0.8 % in the Dolgans and Nganasans, and 3.5 % among the Russians ( p < 0.01). Analysis of the prevalence of the MASP2 genotypes has shown the predominance of the homozygous variant AA in all studied populations, which agrees with the available world data. The heterozygous genotype AG rs72550870 associated with a reduced level of protease was found to occur rarely in the Nenets, Dolgans and Nganasans compared to newborns of Caucasoid origin from Krasnoyarsk: 0.5 % versus 3.3 %, respectively. Moreover, among 323 examined Nenets, one AG carrier was identified, whereas in Russians, 16 out of 242 examined newborns were found to be AG carriers ( p < 0.001). A homozygous variant (GG) in total absence of protease with impaired binding of both MBL and ficolins was not detected in any of the 980 examined newborns. An additional analysis of infectious morbidity in Arctic populations allows one to find phenotypic characteristics related to a high functional activity of the lectin pathway of complement activation as an most important factor for the first-line of anti-infectious defense, including such new viral diseases as COVID-19.

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Frequency and distribution of FCN2 and FCN3 functional variants among MBL2 genotypes

Cited by 14 publications

References 88 publications

Novel Polymorphism in a Promoter of MBL2 Gene Result in Lower MBL Expression in Chronic Infection Caused by HCV

Novel Polymorphism in a Promoter of MBL2 Gene Result in Lower MBL Expression in Chronic Infection Caused by HCV

European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) Complement Guideline: Deficiencies, Diagnosis, and Management

Prevalence of the polymorphic H-ficolin (FCN3) genes and mannosebinding lectin-associated serine protease-2 (MASP2) in indigenous populations from the Russian Arctic regions

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