A study of genes encoding cytokines (IL6, IL10, TNF), cytokine receptors (IL6R, IL6ST), and glucocorticoid receptor (NR3C1) and susceptibility to bronchopulmonary dysplasia

BMC Medical Genetics

Mikko Hallman⁴  Pascal M Lavoie⁶  Mika Rämet²  Outi Tammela³  Gergely Toldi⁷  Sture Andersson¹  M Anneli Kari¹  Ritva Haataja⁵  Mari Mahlman⁴  Minna K Karjalainen⁴  Johanna M Huusko⁴ 

[1] Children’s Hospital, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland;BioMediTech, University of Tampere, Tampere, Finland;Department of Pediatrics, Tampere University Hospital, Tampere, Finland;Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland;Biocenter Oulu, Oulu, Finland;Child and Family Research Institute of British Columbia, Vancouver, Canada;First Department of Pediatrics, Semmelweis University, Budapest, Hungary

关键词: Single nucleotide polymorphism;    Preterm infant;    Interleukin;    Glucocorticoid receptor;    Epistasis;    Bronchopulmonary dysplasia;   

Others  :  1090265
DOI  :  10.1186/s12881-014-0120-7

 received in 2014-06-24, accepted in 2014-10-13,  发布年份 2014

【 摘 要 】

Background

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease associated with very preterm birth. The major risk factors include lung inflammation and lung immaturity. In addition, genetic factors play an important role in susceptibility to moderate-to-severe BPD. In this study, the aim was to investigate whether common polymorphisms of specific genes that are involved in inflammation or differentiation of the lung have influence on BPD susceptibility.

Methods

Genes encoding interleukin-6 (IL6) and its receptors (IL6R and IL6ST), IL-10 (IL10), tumor necrosis factor (TNF), and glucocorticoid receptor (NR3C1) were assessed for associations with moderate-to-severe BPD susceptibility. Five IL6, nine IL6R, four IL6ST, one IL10, two TNF, and 23 NR3C1 single nucleotide polymorphisms (SNPs) were analyzed in very preterm infants born in northern Finland (56 cases and 197 controls) and Canada (58 cases and 68 controls). IL-6, TNF and gp130 contents in umbilical cord blood, collected from very preterm infants, were studied for associations with the polymorphisms. Epistasis (i.e., interactions between SNPs in BPD susceptibility) was also examined. SNPs showing suggestive associations were analyzed in additional replication populations from Finland (39 cases and 188 controls) and Hungary (29 cases and 40 controls).

Results

None of the studied SNPs were associated with BPD nor were the IL6, TNF or IL6ST SNPs associated with cord blood IL-6, TNF and gp130, respectively. However, epistasis analysis suggested that SNPs in IL6ST and IL10 were associated interactively with risk of BPD in the northern Finnish population; however, this finding did not remain significant after correction for multiple testing and the finding was not replicated in the other populations.

Conclusions

We conclude that the analyzed SNPs within IL6, IL6R, IL6ST, IL10, TNF, and NR3C1 were not associated with BPD. Furthermore, there was no evidence that the studied SNPs directly contribute to the cord blood protein contents.

【 授权许可】

   
2014 Huusko et al.; licensee BioMed Central Ltd.

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