Aquaporin-1 and aquaporin-9 gene variations in sudden infant death syndrome

Siri Hauge Opdal,Linda Ferrante,Torleiv Ole Rognum,Arne Stray-Pedersen

doi:10.1007/s00414-020-02493-9

Siri Hauge Opdal, Linda Ferrante + Show 2 more

Open Access

https://doi.org/10.1007/s00414-020-02493-9

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Abstract

Several studies have indicated that a vulnerability in the development and regulation of brain function is involved in sudden infant death syndrome (SIDS). The aim of this study was to investigate the genes encoding the brain aquaporins (AQPs) AQP1 and AQP9 in SIDS. The hypothesis was that specific variants of these genes are part of the genetic vulnerability predisposing infants to sudden unexpected death. The study included 168 SIDS cases with a median age of 15.5 (range 2–52) weeks and 372 adolescent/adult deceased controls with a median age of 44 (range 11–91) years. In the AQP1 gene, the rs17159702 CC/CT genotypes were found to be associated with SIDS (p = 0.02). In the AQP9 gene, the combination of a TT genotype of rs8042354, rs2292711 and rs13329178 was more frequent in SIDS cases than in controls (p = 0.03). In the SIDS group, an association was found between genetic variations in the AQP1 gene and maternal smoking and between the 3xTT combination in the AQP9 gene and being found lifeless in a prone position. In conclusion, this study adds further evidence to the involvement of brain aquaporins in SIDS, suggesting that specific variants of AQP genes constitute a genetic predisposition, making the infant vulnerable to sudden death together with external risk factors and probably other genetic factors.

Highlights

Sudden infant death syndrome (SIDS) is defined as the sudden unexpected death of an infant less than 1 year of age, with the onset of the fatal episode apparently occurring during sleep, and which remains unexplained after a thorough investigation, including a complete autopsy and a review of the circumstances of the death and the clinical history [1].Several studies have indicated that a vulnerability in the development and regulation of brain function is involved in SIDS [2,3,4,5]
It was found that specific variants of the gene encoding AQP1 were more frequent in SIDS cases than in controls (Table 2)
AQP1 is present at an early stage in the developing human foetus, and during the early foetal period (8–12 weeks), the third and fourth ventricles of the choroid plexus show strong apical AQP1 staining [30]

Summary

Introduction

Several studies have indicated that a vulnerability in the development and regulation of brain function is involved in SIDS [2,3,4,5]. Aquaporins (AQPs) are a group of proteins that function as water channels; they facilitate the rapid transport of water and other solutes across the plasma membrane. It has been reported that a lack of AQP4 expression is paralleled by abnormally high levels of 5-HT in various areas of the brain [11]. This may indicate that a well-functioning water balance is important for the regulation of neurotransmitters, suggesting a possible explanation for the 5-HT imbalances observed in SIDS [7]

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