Delnaz Fard1, Katharina Läer1, Thomas Rothämel1, Peter Schürmann2, Matthias Arnold3, Marta Cohen4, Mechtild Vennemann5, Heidi Pfeiffer5, Thomas Bajanowski6, Arne Pfeufer3, Thilo Dörk2, Michael Klintschar7. 1. Institute of Legal Medicine, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany. 2. Gynaecology Research Unit, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany. 3. Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany. 4. Sheffield Children's Hospital NHS Trust, Western Bank, Sheffield, S10 2TH, UK. 5. Institute of Legal Medicine, Universität Münster, Roentgenstr. 23, 48149, Münster, Germany. 6. Institut of Legal Medicine, Universität Essen, Hufelandstr. 55, 45122, Essen, Germany. 7. Institute of Legal Medicine, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany. Klintschar.Michael@mh-hannover.de.
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.
BACKGROUND:Sudden infant death syndrome (SIDS) causes early infantdeath 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.
Entities:
Keywords:
Association study; Genetic predisposition; Infection; Mannose-binding lectin; Polymorphism; SIDS
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