Polymorphisms of the FCN2 Gene 3’UTR Region and Their Clinical Associations in Preterm Newborns

Świerzko, Anna St.; Jarych, Dariusz; Gajek, Gabriela; Chojnacka, Karolina; Kobiela, Paulina; Kufelnicka-Babout, Maja; Michalski, Mateusz; Sobczuk, Katarzyna; Szala-Poździej, Agnieszka; Matsushita, Misao; Mazela, Jan; Domżalska-Popadiuk, Iwona; Kilpatrick, David C.; Kalinka, Jarosław; Sekine, Hideharu; Cedzyński, Maciej

doi:10.3389/fimmu.2021.741140

Cited by 5 publications

(15 citation statements)

References 52 publications

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“…The study group comprised 501 Polish preterm newborns born in the Department of Newborns’ Infectious Diseases (University of Medical Sciences, Poznań, Poland), Department of Neonatology (Medical University of Gdańsk, Gdańsk, Poland) and Department of Perinatology (Medical University of Łódź, Łódź, Poland) [ 4 ]. Among them, 105 were born at gestational age < 33 weeks (mean: 30.3 ± 1.9; range: 24–32) and 396 were born between the 33rd and 37th week of gestation (mean: 35 ± 1.1).…”

Section: Methodsmentioning

confidence: 99%

“…A total of 323 newborns came from singleton pregnancies, 172 from 97 twin pregnancies (in 22, material from only one sibling was collected) and 6 from 2 triple pregnancies. Data concerning the FCN2 gene 3′UTR polymorphisms, concentrations of ficolin-2 in cord sera and their clinical associations were published recently [ 4 ]. However, 3 subjects were excluded from current analyses due to incomplete results of promoter SNP analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Possession of variant alleles at positions −986 (rs3124952, A > G) and −64 (rs7865453, A > C) is related to lower ficolin-2 levels, while minor alleles at positions −602 (rs3124953, G > A) and −4 (rs17514136, A > G) have the opposite effect [ 1 , 2 , 3 ]. The above-mentioned SNPs were shown to form 2 haplotype blocks: one created by rs3124952 and rs3124953, and another, by rs7865453 and rs17514136 [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Our previous data suggested that low ficolin-2 concentration (determined in cord serum) is associated with prematurity, low birthweight and perinatal infections [ 15 ]. Recently, we reported for the first time a relationship between SNPs of the FCN2 gene 3′-untranslated region (3′UTR) and very low (≤1500 g) birthweight as well as early onset of infection and pneumonia in preterm newborns [ 4 ]. Furthermore, two of the 3′UTR polymorphisms (rs4521835 and rs73664188) influenced ficolin-2 concentration in cord sera [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we reported for the first time a relationship between SNPs of the FCN2 gene 3′-untranslated region (3′UTR) and very low (≤1500 g) birthweight as well as early onset of infection and pneumonia in preterm newborns [ 4 ]. Furthermore, two of the 3′UTR polymorphisms (rs4521835 and rs73664188) influenced ficolin-2 concentration in cord sera [ 4 ]. Here, we report associations of the aforementioned promoter region polymorphism with short gestational age and very low birthweight in the same cohort.…”

Section: Introductionmentioning

confidence: 99%

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Association of the FCN2 Gene Promoter Region Polymorphisms with Very Low Birthweight in Preterm Neonates

Szala-Poździej

Swierzko

Gajek

et al. 2022

IJMS

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Single nucleotide polymorphisms (SNPs) localised to the promoter region of the FCN2 gene are known to influence the concentration of ficolin-2 in human serum and therefore potentially have clinical associations. We investigated the relationships between SNPs at positions −986 (A > G), −602 (G > A), −64 (A > C) and −4 (A > G) and clinical complications in 501 preterms. Major alleles at positions −986 and −64 and A/A homozygosity for both polymorphisms were less frequent among babies with very low birthweight (VLBW, ≤1500 g) compared with the reference group (OR = 0.24, p = 0.0029; and OR = 0.49, p = 0.024, respectively for A/A genotypes). A lower frequency of G/G homozygosity at position −4 was associated with gestational age <33 weeks and VLBW (OR = 0.38, p = 0.047; and OR = 0.07, p = 0.0034, respectively). The AGAG haplotype was protective for VLBW (OR = 0.6, p = 0.0369), whilst the GGCA haplotype had the opposite effect (OR = 2.95, p = 0.0249). The latter association was independent of gestational age. The AGAG/GGAA diplotype favoured both shorter gestational age and VLBW (OR = 1.82, p = 0.0234 and OR = 1.95, p = 0.0434, respectively). In contrast, AGAG homozygosity was protective for lower body mass (OR = 0.09, p = 0.0155). Our data demonstrate that some FCN2 variants associated with relatively low ficolin-2 increase the risk of VLBW and suggest that ficolin-2 is an important factor for fetal development/intrauterine growth.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Association of the FCN2 Gene Promoter Region Polymorphisms with Very Low Birthweight in Preterm Neonates

Szala-Poździej

Swierzko

Gajek

et al. 2022

IJMS

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Analysis of the distribution of ficolin gene polymorphisms (<I>FCN2</I>) in children with bronchial asthmas of various severity

Smolnikova,

Afonicheva,

Marchenko

et al. 2024

Med. immunol.

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Asthma is one of the most common chronic diseases in all age groups. Asthma has heterogeneous phenotypes with different etiologies. Many parameters are used to classify asthma, for example, the severity and level of flow control. The asthma phenotype is dependent on the state of the immune system, and innate immunity plays an important role in the susceptibility and pathophysiology of asthma. The complement system (CS) consists of a complex of protective proteolytic enzymes (including lectins). Ficolin-2 (L-ficolin) is one of the main opsonizing molecules of respiratory secretions and a protein of the lectin pathway of CS activation. Polymorphisms in the L-ficolin gene affect the level of expression which may be associated with a higher susceptibility to infections and viruses, as well as a predisposition to asthma.Aim: To study the distribution of polymorphisms rs17549193 and rs7851696 of the L-ficolin (FCN2) gene in children with asthma of varying severity.Russian children from the Children’s Allergy Center (Krasnoyarsk, Russia), aged from 8 to 18 years, were studied. Children with asthma were divided into groups depending on the severity of the disease in accordance with GINA-2023: mild (n = 146) and severe (n = 254). The comparison group included children of comparable age and gender without asthma, allergies or infections. DNA extraction from blood was performed using the sorbent method. Genotyping of polymorphisms rs17549193 and rs7851696 FCN2 was performed by real-time polymerase chain reaction.The results obtained provide distribution of the polymorphic variants FCN2 gene in the population of healthy Russian children and in children with a socially and economically important disease, namely asthma. The distribution of rs17549193 and rs7851696 FCN2 corresponds to the global Caucasoid populations. There were no statistically significant differences between asthma patients with varying degrees of severity of the disease and healthy ones in the studied sample.The results indicate an expansion of the sample and range of studied polymorphic genes of proteins of the lectin pathway of CS activation due to their importance for the prevention of severe forms of diseases, as well as their significance in the functioning of the immune system.

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Association of low ficolin-2 concentration in cord serum with respiratory distress syndrome in preterm newborns

Gajek

Swierzko²,

Jarych³

et al. 2023

Front. Immunol.

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IntroductionFicolin-2 is a serum pattern recognition molecule, involved in complement activation via the lectin pathway. This study aimed to investigate the association of ficolin-2 concentration in cord blood serum with complications related to premature birth.Methods546 premature neonates were included. The concentration of ficolin-2 in cord blood serum was determined by a sandwich TRIFMA method. FCN2 genetic variants were analysed with RFLP-PCR, allele-specific PCR, Sanger sequencing or allelic discrimination using TaqMan probes method.FindingsCord blood serum ficolin-2 concentration correlated positively with Apgar score and inversely with the length of hospitalisation and stay at Neonatal Intensive Care Unit (NICU). Multivariate logistic regression analysis indicated that low ficolin-2 increased the possibility of respiratory distress syndrome (RDS) diagnosis [OR=2.05, 95% CI (1.24-3.37), p=0.005]. Median ficolin-2 concentration was significantly lower in neonates with RDS than in premature babies without this complication, irrespective of FCN2 gene polymorphisms localised to promoter and 3’untranslated regions: for patients born <33 GA: 1471 ng/ml vs. 2115 ng/ml (p=0.0003), and for patients born ≥33 GA 1610 ng/ml vs. 2081 ng/ml (p=0.012). Ficolin-2 level was also significantly lower in neonates requiring intubation in the delivery room (1461 ng/ml vs. 1938 ng/ml, p=0.023) and inversely correlated weakly with the duration of respiratory support (R=-0.154, p<0.001). Interestingly, in the neonates born at GA <33, ficolin-2 concentration permitted differentiation of those with/without RDS [AUC=0.712, 95% CI (0.612-0.817), p<0.001] and effective separation of babies with mild RDS from those with moderate/severe form of the disease [AUC=0.807, 95% CI (0.644-0.97), p=0.0002].ConclusionLow cord serum ficolin-2 concentration (especially in neonates born at GA <33 weeks) is associated with a higher risk of developing moderate/severe RDS, requiring respiratory support and intensive care.

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Polymorphisms of the FCN2 Gene 3’UTR Region and Their Clinical Associations in Preterm Newborns

Cited by 5 publications

References 52 publications

Association of the FCN2 Gene Promoter Region Polymorphisms with Very Low Birthweight in Preterm Neonates

Association of the FCN2 Gene Promoter Region Polymorphisms with Very Low Birthweight in Preterm Neonates

Analysis of the distribution of ficolin gene polymorphisms (<I>FCN2</I>) in children with bronchial asthmas of various severity

Association of low ficolin-2 concentration in cord serum with respiratory distress syndrome in preterm newborns

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