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.
The aim of this study was to investigate if a range of known rare and common genetic variants in the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88) pathway were present or overrepresented in sudden infant death syndrome (SIDS) compared to controls.
<b>Abbreviations</b>: HAS, Haute Autorité de Santé: French National Health Authority; NICHD, National Institute of Child Health and Human Development; PACA, Provence-Alpes-Côte d'Azur region of France; SUID, sudden unexpected infant death; SIDS, sudden infant death syndrome; CépiDc, Centre d'Epidémiologie sur les Causes Médicales de Décès/Center for Epidemiology on the Medical Causes of Death.
This review focuses on the pathways within the medulla involving SP and its tachykinin NK1 receptor, their potential relationship with the medullary 5-HT system, and possible involvement in the pathogenesis of SIDS.
Compared to SIDS I infants, SIDS II infants had greater TUNEL expression in the dorsal motor nucleus of the vagus (p < 0.01) and greater active caspase-9 expression in the medial and spinal vestibular nuclei (p = <0.01).
This review focuses on the pathways within the medulla involving SP and its tachykinin NK1 receptor, their potential relationship with the medullary 5-HT system, and possible involvement in the pathogenesis of SIDS.
Abnormal NK1R binding in these medullary nuclei may contribute to the defective interaction of critical medullary mechanisms with cerebellar sites, resulting in an inability of a SIDS infant to illicit appropriate respiratory and motor responses to life threatening challenges during sleep.
Within the hypothalamus, OxA and Dyn co-localised with a 20 % decrease in expression in SIDS infants (P = 0.001). pPERK and ATF4 expression in OxA neurons were increased by 35 % (P = 0.001) and 15 % (P = 0.001) respectively, with linear relationships between the decreased OxA/Dyn expression and the percentages of co-localised pPERK/OxA and ATF4/OxA evident (P = 0.01, P = 0.01).
The m.3250T>C mutation in MTTL1 has previously been described in a few individuals with a possibly riboflavin-responsive myopathy and an association with sudden infant death syndrome was suspected.
Our results suggest that PNE is capable of aggravating the SLCF-mediated apnea and bradycardia through TRPV1 sensitization and neuronal excitation, which may contribute to the pathogenesis of SIDS.-Gao, X., Zhao, L., Zhuang, J., Zang, N., Xu, F. Prenatal nicotinic exposure prolongs superior laryngeal C-fiber-mediated apnea and bradycardia through enhancing neuronal TRPV1 expression and excitation.
Alterations in the GFI1 expression might be linked to various conditions that are known to be associated with SIDS, such as dysregulated hematopoiesis and excessive inflammatory response.
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.
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).
However, using a single unstable reference gene for normalization resulted in no significant differences in transcript abundance of RPS27A between SIDS and the controls.
The determined genotype frequencies were SSTR2: CC (14.4 %), CG (49.7 %), GG (35.9 %) in controls and CC (17.1 %), CG (49.1 %), and GG (33.8 %) in SIDS; P2RY1: AA (70.6 %), AG (28.7 %), GG (0.7 %) in SIDS and AA (68.3 %), AG (27.9 %), and GG (3.8 %) in the control group.
Being found dead in the prone position (a known risk factor for SIDS) was related to a lower HSPA1B up-regulation in SIDS compared to SIDS found on their side or back.
The results suggest that the pathogenic variant of rs72466451 may play a role in a subgroup of SIDS cases with impaired Hsp60-mediated stress response.
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.