Role of Fibronectin-1 polymorphism genes with the pathogenesis of intraventricular hemorrhage in preterm infants

Abstract

Background/introduction Intraventricular hemorrhage (IVH) is a dangerous complication facing a significant proportion of preterm infants. It is multifactorial in nature, and an observed fibronectin deficiency in the germinal matrix basal lamina is among the most prominent factors that influence such rupture. Better understanding of the FN1 gene polymorphisms and their role in IVH may further clarify the presence of a genetic susceptibility of certain babies to this complication. The aim of this study was to assess if 5 single nucleotide polymorphisms of the fibronectin gene may be linked to an increased incidence of IVH. Material and methods The study included 108 infants born between 24 and 32 weeks of gestation. IVH was diagnosed using cranial ultrasound performed on the 1st,3rd, and 7th day after birth and classified according to Papile et al. IVH classification. The 5 FN1 gene polymorphisms assessed in the study were the following: rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655. Results IVH developed in 51 (47.2%) out of the 108 preterm infants. This includes, 18 (35.3%) with stage I IVH, 19 (37.3%) with stage II, 11 (21.6%) with stage III, and 3 (5.9%) with stage IV IVH. Incidence of IVH was higher in infants with lower APGAR scores, low gestational age, and low birthweight. Analysis showed that IVH stage II to IV was approximately seven times more likely to occur in infants with the genotype TT FN1 rs10202709 (OR 7237 (1046-79.59; p = 0,044)). No other significant association was found with the rest of the polymorphisms. Conclusion The results of our study indicate a sevenfold increased genetic susceptibility to IVH in preterm infants with the TT FN1 rs10202709 gene polymorphism. The fibronectin gene polymorphism may therefore be of crucial importance as a genetic risk factor for IVH in preterm infants. Further studies are warranted.

Prevalence of intraventricular haemorrhage and determinants of its early outcomes among preterm neonates at the newborn unit of a teaching hospital in Western Kenya

“…This IVH prevalence finding is lower than that reported in a Polish prospective study [16] among 108 newborns studied, a difference that could be attributed to a lower sample size in the Poznan University of Medical Sciences teaching hospital study. Although both studies were conducted at a teaching hospital, when a lower sample size is adopted, there is a greater likelihood of having a higher proportion of the factor of interest compared to findings in larger hospital or community-based studies conducted over a longer period.…”

Polymorphisms of fibronectin-1 (rs3796123; rs1968510; rs10202709; rs6725958; and rs35343655) are not associated with bronchopulmonary dysplasia in preterm infants

“…Polymorphisms and mutations in the FN1 gene have a multimodal association and have been shown to play a role in renal glomerulopathy, spondylometaphyseal dysplasia, lung brosis in systemic sclerosis, knee osteoarthritis, lung cancers, gastric cancers, breast cancers, and schizophrenia [24], [25], [14], [26], [27], [28], [29], [30], [31]. Considering the relationship of single nucleotide polymorphisms of bronectin in neonatal diseases, so far only an association between bronectin-1 SNP and IVH has been described [32]. Although pathogenesis of IVH is heterogeneous, undoubtedly the fragility of germinal matrix microvasculature plays an instrumental role in its pathology [33].…”

“…Such reduction of bronectin levels shows further potential for affecting developmental processes and the stability of cellular structure and architecture [36]. There are many studies that show the signi cant role that genetics plays in the pathogenesis of BPD [32]. A plethora of data reveal that genetic differences are variable between different ethnic groups.…”

Role of Single Nucleotide Fibronectin Polymorphisms in Pathogenesis of Bronchopulmonary Dysplasia

“…Polymorphisms and mutations in the FN1 gene have a multimodal association and have been shown to play a role in renal glomerulopathy, spondylometaphyseal dysplasia, lung fibrosis in systemic sclerosis, knee osteoarthritis, lung cancers, gastric cancers, breast cancers, and schizophrenia [24], [25], [14], [26], [27], [28], [29], [30], [31]. Considering the relationship of single nucleotide polymorphisms of fibronectin in neonatal diseases, so far only an association between fibronectin-1 SNP and IVH has been described [32]. Although pathogenesis of IVH is heterogeneous, undoubtedly the fragility of germinal matrix microvasculature plays an instrumental role in its pathology [33].…”

“…Such reduction of fibronectin levels shows further potential for affecting developmental processes and the stability of cellular structure and architecture [36]. There are many studies that show the significant role that genetics plays in the pathogenesis of BPD [32]. A plethora of data reveal that genetic differences are variable between different ethnic groups.…”