Gene variants associated with obstructive sleep apnea (OSA) in relation to sudden infant death syndrome (SIDS)

Abstract

Background Both obstructive sleep apnea (OSA) and (at least a fraction of) sudden infant death syndrome (SIDS) are associated with impaired respiration. For OSA, an association with several gene variants was identified. Therefore, our hypothesis is that these polymorphisms might be of relevance in SIDS as well. Methods Twenty-four single nucleotide polymorphisms (SNPs) in 21 candidate genes connected to OSA, were genotyped in a total of 282 SIDS cases and 374 controls. Additionally, subgroups based on factors codetermining the SIDS risk (age, sex, season, and prone position) were established and compared as well. Results Two of the analyzed SNPs showed nominally significant differences between SIDS and control groups: rs1042714 in ADRB2 (adrenoceptor beta 2) and rs1800541 in EDN1 (endothelin 1). In the subgroup analyses, 10 further SNPs gave significant results. Nevertheless, these associations did not survive adjustment for multiple testing. Conclusions Our results suggest that there might be a link between SIDS and OSA and its resulting respiratory and cardiovascular problems, albeit this predisposition might be dependent on the combination with other, hitherto unknown gene variants. These findings may encourage replication studies to get a better understanding of this connection.

Obstructive sleep apnea and associated factors among hypertensive patients attending a tertiary cardiac center in Tanzania: a comparative cross-sectional study

“…Furthermore, studies involving monozygotic twins and siblings/children of persons with OSA have shown an up-to 50% increased odds of developing OSA compared to the general population (Ferini-Strambi et al 1995;Friberg et al 2009;Lundkvist et al 2012;Szily et al 2019). Additionally, numerous genetic studies (Palmer et al 2003;Patel et al 2007;Khalyfa et al 2008;Gozal et al 2007;Kalra et al 2008;Farias Tempaku et al 2020;Maierean et al 2021;Kerz et al 2021;Patel et al 2012) have identified several novel genetic loci associated with a sleep apnea phenotype suggesting around two-fifth (Casale et al 2009;Yue et al 2008;Yue et al 2005) of the OSA variance is attributable to genetic factors.…”

Polymorphisms of the hypothalamic–pituitary–adrenal axis may lead to an inadequate response to stress and contribute to sudden infant death syndrome

“…Their mean age was 31 years (range: 18–48 years). Genomic deoxyribonucleic acid from blood samples was extracted using the QIAampDNA Mini Kit (Qiagen) as described 17 . The first step to selecting the appropriate loci was to establish a list of genes that were relevant to the HPA axis, including receptors and biosynthesis enzymes.…”

“…The allele‐specific SNP type assays were typed on 192.24 Genotyping Dynamic Arrays using the Biomark EP1 platform (Fluidigm Corp), as previously described 17 …”

“…Univariate logistic regression analyses were performed to evaluate the overall association, with STATA12 (StataCorp LLC). The samples were grouped into three different subcategories for the stratified analyses, according to parameters that are known to increase the risk of SIDS, as previously demonstrated 17 . These included an analysis based on gender, age at death and season of death.…”

“…Genomic deoxyribonucleic acid from blood samples was extracted using the QIAampDNA Mini Kit (Qiagen) as described. 17 The first step to selecting the appropriate loci was to establish a list of genes that were relevant to the HPA axis, including receptors and biosynthesis enzymes. Then, the Single Nucleotide Polymorphism Database was searched to identify variants that either had functional consequences or had been associated with clinical findings.…”