BACKGROUND: Excessive release of tumour necrosis factor (TNF) may contribute to the pathogenesis of bronchopulmonary dysplasia (BPD) in very preterm infants. It has been proposed that the risk of developing BPD may be associated with host genetic factors that regulate TNF production. The most commonly studied variant is the guanine to adenine transition at position -308 nucleotides relative to the transcription start site (TNF -308A). However, studies that have examined the association between TNF (-308A) and BPD have reported conflicting findings and have been generally underpowered to exclude plausible genotypic risks. AIM: To systematically review evidence for the association of TNF (-308A) with BPD. METHODS: Systematic review and meta-analysis of genetic association studies. RESULTS: Six cohort studies in which a total of 804 preterm infants participated were identified. The studies were generally of fair methodological quality. None of the individual studies or a fixed-effects meta-analysis of the six studies found a significant association of TNF (-308A) genotype with the development of BPD: pooled relative risk 1.03 (95% CI 0.85 to 1.25). CONCLUSIONS: These data suggest that the TNF (-308A) polymorphism is not strongly associated with the risk of developing BPD in very preterm infants. The 95% confidence interval is consistent with an association no stronger than a relative increase in risk of 25%. Future research efforts to define genetic predisposition to BPD should focus on alternative candidate genes.
BACKGROUND: Excessive release of tumour necrosis factor (TNF) may contribute to the pathogenesis of bronchopulmonary dysplasia (BPD) in very preterm infants. It has been proposed that the risk of developing BPD may be associated with host genetic factors that regulate TNF production. The most commonly studied variant is the guanine to adenine transition at position -308 nucleotides relative to the transcription start site (TNF -308A). However, studies that have examined the association between TNF (-308A) and BPD have reported conflicting findings and have been generally underpowered to exclude plausible genotypic risks. AIM: To systematically review evidence for the association of TNF (-308A) with BPD. METHODS: Systematic review and meta-analysis of genetic association studies. RESULTS: Six cohort studies in which a total of 804 preterm infants participated were identified. The studies were generally of fair methodological quality. None of the individual studies or a fixed-effects meta-analysis of the six studies found a significant association of TNF (-308A) genotype with the development of BPD: pooled relative risk 1.03 (95% CI 0.85 to 1.25). CONCLUSIONS: These data suggest that the TNF (-308A) polymorphism is not strongly associated with the risk of developing BPD in very preterm infants. The 95% confidence interval is consistent with an association no stronger than a relative increase in risk of 25%. Future research efforts to define genetic predisposition to BPD should focus on alternative candidate genes.
Authors: Johanna M Huusko; Minna K Karjalainen; Mari Mahlman; Ritva Haataja; M Anneli Kari; Sture Andersson; Gergely Toldi; Outi Tammela; Mika Rämet; Pascal M Lavoie; Mikko Hallman Journal: BMC Med Genet Date: 2014-11-01 Impact factor: 2.103