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

Szala-Poździej, Agnieszka; Swierzko, Anna; Gajek, Gabriela; Kufelnicka-Babout, Maja; Chojnacka, Karolina; Kobiela, Paulina; Jarych, Dariusz; Sobczuk, Katarzyna; Mazela, Jan; Domżalska-Popadiuk, Iwona; Kalinka, Jarosław; Sekine, Hideharu; Matsushita, Misao; Cedzyński, Maciej

doi:10.3390/ijms232315336

Cited by 3 publications

(7 citation statements)

References 39 publications

(48 reference statements)

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“…Our data confirmed association of the FCN2 gene promoter polymorphisms and ficolin-2 concentration, published previously by others and ourselves ( 20 , 28 , 52 ). We previously reported also the relationship of 3’UTR diplotypes (group VI) with low ficolin-2 ( 21 ).…”

Section: Discussionsupporting

confidence: 93%

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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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Section: Discussionsupporting

confidence: 93%

“…The differences in ficolin-2 levels were analysed in the context of the FCN2 gene promoter haplotype GGCA [corresponding to single nucleotide polymorphisms at positions: -986 (rs3124952); -602 (rs3124953); -64 (rs7865453); -4 (rs17514136)] ( 28 ) and 3’UTR group VI diplotype ( 21 ), both associated with low ficolin-2 concentration.…”

Section: Methodsmentioning

confidence: 99%

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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“…The GGCA haplotype had the opposite effect, independently of GA. Finally, the AGAG/GGAA diplotype was associated with both shorter (<33 weeks) GA and body mass at birth <1500 g ( 174 ). Earlier, Kilpatrick et al.…”

Section: Clinical Associations Of Ficolins In the Neonatementioning

confidence: 94%

“…Recently, Szala-Poździej et al. ( 174 ) reported associations of SNPs localised to the FCN2 gene promoter with birthweight and/or gestational age in Polish preterm babies. Major alleles for rs3124952 (-986 A>G), rs7865453 (-64 A>C) and A/A homozygosity for both mentioned SNP were found less frequently among newborns with very low birthweight (VLBW, ≤1500 g) compared with the corresponding reference group.…”

Section: Clinical Associations Of Ficolins In the Neonatementioning

confidence: 99%

Collectins and ficolins in neonatal health and disease

Cedzyński,

Świerzko

2023

Front. Immunol.

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The immune system starts to develop early in embryogenesis. However, at birth it is still immature and associated with high susceptibility to infection. Adaptation to extrauterine conditions requires a balance between colonization with normal flora and protection from pathogens. Infections, oxidative stress and invasive therapeutic procedures may lead to transient organ dysfunction or permanent damage and perhaps even death. Newborns are primarily protected by innate immune mechanisms. Collectins (mannose-binding lectin, collectin-10, collectin-11, collectin-12, surfactant protein A, surfactant protein D) and ficolins (ficolin-1, ficolin-2, ficolin-3) are oligomeric, collagen-related defence lectins, involved in innate immune response. In this review, we discuss the structure, specificity, genetics and role of collectins and ficolins in neonatal health and disease. Their clinical associations (protective or pathogenic influence) depend on a variety of variables, including genetic polymorphisms, gestational age, method of delivery, and maternal/environmental microflora.

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“…Szala-Poździej et al [ 14 ] reported that some FCN2 gene promoter region polymorphisms that are associated with relatively low serum levels of ficolin-2 significantly increase the risk of very low birthweight in preterm neonates.…”

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confidence: 99%