Evidence for an association of interferon gene variants with sudden infant death syndrome

Abstract

Background

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.

Methods

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.

Results

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).

Conclusion

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.

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Corresponding author

Correspondence to Michael Klintschar.

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The local ethics committee at Hannover Medical School has approved this study.

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Electronic supplementary material

Supplementary Figure S3
figure1

Meta-analysis rs2069727 (Hannover study) with rs2430561 (Moscovis) (Mantel-Haenszel OR 0,79, 95% CI 0.64; 0.97, p = 0.02. OR, odds ratio; 95%CI, 95% confidence. (PNG 5 kb)

Supplementary Figure S1

Genotyping results for IFNG variants rs2069705, rs2069718 and rs2069727, each in a run consisting of 190 samples are given as an example. Gray samples could not be successfully typed, blue and red samples correspond to the homozygous genotypes, green samples to the heterozygous genotype. (PNG 1093 kb)

Supplementary Figure S2

Association network for proteins modulated by the investigated genes of this study. (DOCX 169 kb)

High resolution image (TIF 718 kb)

Supplementary Table 1

Allele frequencies in controls and SIDS cases for each analyzed variant. (DOCX 16 kb)

Supplementary Table 2

Full names of genes and abbreviations are listed. (DOCX 13 kb)

Supplementary Table 3

All SNPs are listed with their chromosome position, alleles, functional consequences and corresponding studies that have shown any effects of these SNPs. (DOCX 17 kb)

ESM 1

(DOCX 16 kb)

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Hafke, A., Schürmann, P., Rothämel, T. et al. Evidence for an association of interferon gene variants with sudden infant death syndrome. Int J Legal Med 133, 863–869 (2019). https://doi.org/10.1007/s00414-018-1974-6

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Keywords

  • SIDS
  • Infection
  • Genetic predisposition
  • Interferon
  • Polymorphism
  • Association study