International Journal of Legal Medicine

, Volume 130, Issue 4, pp 1025–1033 | Cite as

Candidate gene variants of the immune system and sudden infant death syndrome

  • Delnaz Fard
  • Katharina Läer
  • Thomas Rothämel
  • Peter Schürmann
  • Matthias Arnold
  • Marta Cohen
  • Mechtild Vennemann
  • Heidi Pfeiffer
  • Thomas Bajanowski
  • Arne Pfeufer
  • Thilo Dörk
  • Michael Klintschar
Original Article

Abstract

Background

Sudden infant death syndrome (SIDS) causes early infant death with an incidence between 0.5 and 2.5 cases among 1000 live births. Besides central sleep apnea and thermal dysregulation, infections have been repeatedly suggested to be implicated in SIDS etiology.

Methods

To test the risk contribution of common genetic variants related to infection, we genotyped 40 single-nucleotide polymorphisms (SNPs) from 15 candidate genes for association with SIDS in a total of 579 cases and 1124 controls from Germany and the UK in a two-stage case control design.

Results

The discovery-stage series (267 SIDS cases and 303 controls) revealed nominally significant associations for variants in interleukin 6 (IL6) (rs1880243), interleukin 10 (IL10) (rs1800871, rs1800872), and mannose-binding lectin 2 (MBL2) (rs930506), and for several other variants in subgroups. Meta-analyses were then performed in adding genotype information from a genome-wide association study of another 312 European SIDS cases and 821 controls. Overall associations were observed for two independent variants in MBL2: rs930506 in a co-dominant model (odds ratio (OR) = 0.82, p = 0.04) and rs1838065 in a dominant model (OR = 1.27, p = 0.03).

Conclusion

Our study did not replicate published associations of IL10 variants with SIDS. However, the evidence for two independent MBL2 variants in the combined analysis of two large series seems consistent with the hypothesis that infection may play a role in SIDS pathogenesis.

Keywords

SIDS Infection Genetic predisposition Mannose-binding lectin Polymorphism Association study 

Supplementary material

414_2016_1347_MOESM1_ESM.pdf (149 kb)
Online Resource 1Study design. From 65 intended SNPs, 46 were successfully designed as a SNPtype assay. Six of them dropped out of the study because of poor clustering. Accordingly, 40 SNPs were part of the discovery and replication stage. A list of all 65 SNPs with rs codes is provided in the Study design. QC, Quality control (PDF 148 kb)
414_2016_1347_MOESM2_ESM.pdf (104 kb)
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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Delnaz Fard
    • 1
  • Katharina Läer
    • 1
  • Thomas Rothämel
    • 1
  • Peter Schürmann
    • 2
  • Matthias Arnold
    • 3
  • Marta Cohen
    • 4
  • Mechtild Vennemann
    • 5
  • Heidi Pfeiffer
    • 5
  • Thomas Bajanowski
    • 6
  • Arne Pfeufer
    • 3
  • Thilo Dörk
    • 2
  • Michael Klintschar
    • 1
  1. 1.Institute of Legal MedicineHannover Medical SchoolHannoverGermany
  2. 2.Gynaecology Research UnitHannover Medical SchoolHannoverGermany
  3. 3.Institute of Bioinformatics and Systems BiologyHelmholtz Zentrum München – German Research Center for Environmental HealthNeuherbergGermany
  4. 4.Sheffield Children’s Hospital NHS Trust, Western BankSheffieldUK
  5. 5.Institute of Legal MedicineUniversität MünsterMünsterGermany
  6. 6.Institut of Legal MedicineUniversität EssenEssenGermany

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