Influence of single nucleotide polymorphisms (SNPs) in immunoregulatory genes in the morbidity of preterm newborns

Abstract

Background

Prematurity is the main cause of perinatal and neonatal morbidity and mortality worldwide. Single nucleotide polymorphisms (SNPs) have been associated with the pathogenesis of morbidities in preterm neonates. We aimed to investigate the association between SNPs in regulatory genes of innate immune response IL1B, IL6, IL6R, IL10, TNFA, TNFRII, TLR2 and TLR4 and neonatal/infant morbidities in preterm newborns.

Methods

Oral swabs were collected from 272 newborns (91 preterm and 181 at term) seen at Botucatu Medical School, Unesp, between 2013 and 2014 and SNPs were identified using Taqman^® Genotyping Assays. Medical records were examined to obtain data regarding neonatal/infant morbidity. Stepwise binomial logistic regression models were used to explain the morbidities.

Results

Minor neonatal morbidity was influenced by the clinical parameters of maternal age and newborn weight at birth and by the presence of the allele IL6R2 C (rs2228145) while major neonatal morbidity was only influenced by gestational age. Minor infant morbidity was associated with the allele TLR2 T (rs4696480) and major infant morbidity was associated with gestational age and presence of IL6R2 C.

Conclusion

The presence of SNPs that exacerbate the inflammatory response increases the susceptibility to neonatal and infant morbidity.

Keywords:

• Infant morbidity
• innate immunity genes
• neonatal morbidity
• prematurity
• single nucleotide polymorphisms

Acknowledgments

We would like to thank all the patients enrolled in this study.

Ethics approval and consent to participate

The research project was approved by the Research Ethics Committee Board of Botucatu Medical School, Unesp, under the protocol 3858–2011. Written informed consent was obtained from all the mothers for access to their children’s medical records and collection of the oral swabs, as these samples were collected specifically for this study.

Disclosure 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.

Availability of data and materials

Data generated or analyzed during this study are included in this published article and addendum.

Additional information

Funding

This study was supported by São Paulo Research Foundation (FAPESP) [grants 2011/09433-1 – developmental funds granted to Dr. MGS of the Department of Pathology and 2011/08083-7 – granted to BRAR, Ph.D. Student of Graduate Program in Pathology]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.