Sudden infant death syndrome (SIDS) is a multifactorial syndrome and assumingly, among other mechanisms, a deficit in respiratory control leads to a failure of arousal and autoresuscitation when the child is challenged by a stressful homeostatic event, e.g., hypoxia. We hypothesize that genetic polymorphisms involved in respiratory control mediated in the medulla oblongata contribute to SIDS. Therefore, a total of 366 SIDS cases and 421 controls were genotyped for 48 SNPs in 41 candidate genes. Genotyping was performed using Fluidigm nanofluidic technology. Results were obtained for 356 SIDS and 406 controls and 38 SNPs. After correction for multiple testing, one SNP retained a nominally significant association with seasonal SIDS: rs1801030 in the phenol sulfotransferase 1A1 gene (subgroup: death occurring during summer). A borderline association could be also observed for rs563649 in the opioid receptor μ1 gene in a recessive model (subgroup: death occurring during autumn). As a conclusion, although these data suggest two SNPs to be associated with different subgroups of SIDS cases, none of them can fully explain the SIDS condition, consistent with its multifactorial etiology. Given the great complexity of respiratory control and our initial findings reported here, we believe it is worthwhile to further investigate genes involved in the respiratory system.

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.

We think that allele G provides a protective effect in events of ventilatory stress. Moreover, the significant lack of P2Y1 G allele homozygotes in the SIDS group shows that respiratory response plays an important role in the etiology of SIDS. Thus, we believe it is worthwhile to further investigate functional polymorphisms within genes that are involved in respiratory control in the future.

Aim: It has been suggested that progressive adenosine triphosphate (ATP) depletion could play a key role in sudden infant death syndrome (SIDS). Because mitochondrial deoxyribonucleic acid (mtDNA) codes for a subset of essential genes for oxidative phosphorylation, we investigated 22 mtDNA polymorphisms in a large sample of Caucasian SIDS cases.Methods: A total of 774 samples were analysed, 365 from infant SIDS cases (mean age 131 days) and 409 from controls. These were investigated for the presence of 22 haplogroup-specific single nucleotide polymorphisms (SNPs), using a SNaPshot assay, a mini-sequencing assay that combines polymerase chain reaction (PCR) and sequencing.Results: No significant differences in assigned haplogroups could be detected between the groups. With regard to gender and age, we found significant correlations for SNP positions 3010, 8251, 13 708, 14 470, 15 904 and 16 519. The most prominent result was the A allele in SNP 14 470 in male SIDS cases (p = 0.01).Conclusion: This is the largest study on mtDNA polymorphisms in SIDS to date, and our results indicate that mtDNA may play a role in a subset of SIDS cases. In order to complement these significant results, it is important to consider nuclear gene coding for mitochondrial proteins in future studies.

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