Evidence for an association of interferon gene variants with sudden infant death syndrome
There is evidence that inflammation plays a role in the etiology of sudden infant death syndrome (SIDS). Immune system dysregulation seems to be the background of higher infection susceptibility in SIDS infants. This phenotype is possibly determined by genetic factors.
Twenty-three single nucleotide polymorphisms (SNPs) in the following 13 candidate genes governing the immune system were successfully genotyped in 251 Caucasian SIDS cases and 336 controls from Germany: ADAR1, CSF2RB, DDX58, IFNA1, IFNA21, IFNA8, IFNAR2, IFNG, IL6, MX2, OAS1, OAS3, and TNFA. Associations between genotypes and SIDS were then statistically evaluated using logistic regression analyses.
Overall analysis revealed statistically significant results for two variants in interferon gamma (IFNG) (rs2069705: OR 1.40 (1.07; 1.83), p = 0.01; and rs2069727: OR 0.75 (0.59; 0.96), p = 0.02) and for one variant in interferon alpha 8 (IFNA8) (rs1330321: OR 1.85 (1.06; 3.21), p = 0.03). Haplotype analyses identified a three-marker risk IFNG haplotype rs2069727-rs2069718-rs2069705 associated with SIDS (OR = 1.62, 95% CI 1.23–2.13; p = 0.0003). Subgroup associations were found for variants in adenosine deaminase acting on RNA1 (ADAR1), 2′,5′-oligoadenylate synthetase-1 (OAS1) and colony stimulating factor 2 receptor beta common subunit (CSF2RB).
In summary, this large study of 251 SIDS cases for common variants in 13 candidate genes governing the immune system has provided first evidence for a role of IFNG in the etiology of SIDS and should stimulate further research into the clinicopathological relevance of immunomodulatory genes for this fatal syndrome.
KeywordsSIDS Infection Genetic predisposition Interferon Polymorphism Association study
Compliance with ethical standards
The local ethics committee at Hannover Medical School has approved this study.
- 2.Center for Disease Control and Prevention Sudden unexpected infant death and sudden infant death syndrome. https://www.cdc.gov/sids/data.htm (accessed on 15.12.2017). statistic data from 2015
- 3.Baruteau AE, Tester DJ, Kapplinger JD, Ackerman MJ, Behr ER (2017) Sudden infant death syndrome and inherited cardiac conditions. Nat Rev Cardiol 14(12):715–726. doi: https://doi.org/10.1038/nrcardio.2017.129. Epub 2017 Sep 7, Sudden infant death syndrome and inherited cardiac conditions
- 6.Moon RY, Hauck FR (2018) Risk factors and theories. In: Duncan JR, Byard RW, editors. SIDS Sudden Infant and Early Childhood Death: The Past, the Present and the Future. Adelaide (AU): University of Adelaide Press; May. Chapter 10Google Scholar
- 14.Fard D, Läer K, Rothämel T, Schürmann P, Arnold M, Cohen M, Vennemann M, Pfeiffer H, Bajanowski T, Pfeufer A, Dörk T, Klintschar M (2016) Candidate gene variants of the immune system and sudden infant death syndrome. Int J Legal Med 130(4):1025–1033. https://doi.org/10.1007/s00414-016-1347-y CrossRefPubMedGoogle Scholar
- 17.Jensen LJ, Kuhn M, Stark M, Chaffron S, Creevey C, Muller J, Doerks T, Julien P, Roth A, Simonovic M, Bork P, von Mering C (2009) STRING 8—a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Res 37(Database issue):D412–D416. https://doi.org/10.1093/nar/gkn760 CrossRefPubMedGoogle Scholar