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. 2024 Dec 19:12:1511355.
doi: 10.3389/fped.2024.1511355. eCollection 2024.

Association of TNF-α genetic variants with neonatal bronchopulmonary dysplasia: consolidated results

Seyedeh Elham Shams  1 , Seyed Alireza Dastgheib  2 , Seyede Arefe Mousavi-Beni  3 , Mohamad Hosein Lookzadeh  4 , Seyed Reza Mirjalili  4 , Mohammad Golshan-Tafti  5 , Reza Bahrami  6 , Maryam Yeganegi  7 , Amirhossein Shahbazi  8 , Ali Masoudi  9 , Amirmasoud Shiri  10 , Mahmood Noorishadkam  4 , Hossein Neamatzadeh  4
Affiliations

Association of TNF-α genetic variants with neonatal bronchopulmonary dysplasia: consolidated results

Seyedeh Elham Shams et al. Front Pediatr. .

Abstract

Objectives: Inflammation is increasingly recognized as a key factor in the pathophysiology of bronchopulmonary dysplasia (BPD). While previous research has established significant links between TNF-α polymorphisms and BPD susceptibility, further validation of these associations is needed. This study aims to examine the relationship between TNF-α polymorphisms and the risk of BPD.

Methods: All relevant articles published before October 1, 2024, have been screened in the PubMed, Web of Science, CNKI, and Scopus databases.

Results: A total of 14 case-control studies were conducted: five studies with 1,252 cases and 1,377 controls on -308G/A, three studies with 1,180 cases and 1,194 controls on -238G/A, four studies with 149 cases and 192 controls on -857C/T, and two studies with 82 cases and 162 controls on 1,031 T/C. A significant association was found between the TNF-α -238G/A polymorphism and the risk of BPD. However, no significant relationships were observed for the TNF-α -308G/A, -857C/T, and 1,031 T/C polymorphisms regarding BPD susceptibility.

Conclusions: Our findings indicate a significant association between the TNF-α -238G/A polymorphism and the susceptibility to BPD in preterm neonates, suggesting potential biomarkers for its pathogenesis. However, this meta-analysis has limitations, including possible publication bias and heterogeneity due to the limited number of studies, which may affect the reliability of our conclusions. Moreover, population variability further complicates the interpretation of the link between TNF-α polymorphisms and BPD risk.

Keywords: TNF-α; bronchopulmonary dysplasia; neonate; premature lung diseases; preterm.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of the study selection process, detailing the number of studies identified, screened, assessed for eligibility, and included in the final analysis.
Figure 2
Figure 2
Forest plots illustrating the association between TNF-α polymorphism and BPD risk in preterm infants. Horizontal lines represent 95% CIs for the OR of specific genetic models, with blue circles indicating point estimates of the OR, and a dashed vertical line at OR = 1 for reference.
Figure 3
Figure 3
Funnel plot displaying sensitivity analysis results on the relationship between TNF-α polymorphisms and BPD risk. Blue dots represent the OR for specific genetic models, vertical error bars indicate 95% CIs, and a red dashed line at OR = 1 shows no effect.
Figure 4
Figure 4
Funnel plot demonstrating publication bias in studies on TNF-α polymorphisms and BPD risk in preterm infants: A: −308G/A (recessive model: AA vs. AG + GG); B: −857C/T (dominant model: TT + TC vs. CC). Plots are shown before (blue) and after (red) the “Trim-and-Fill” method application.
Figure 5
Figure 5
Funnel plot depicting the relationship between Z-scores and p-values for publication bias tests (Begg's pBeggs and egger's pEggers) related to TNF-α polymorphisms and BPD risk. The x-axis shows Z-scores indicating effect strength, the y-axis displays corresponding p-values, and a dashed horizontal line at p = 0.05 indicates the threshold for statistical significance.
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