Institute of Legal Medicine, Hannover Medical School, Carl-Neuberg Straße 1, 30625, Hannover, Germany.
Gynaecology Research Unit, Hannover Medical School, Carl-Neuberg Straße 1, 30625, Hannover, Germany.
Acta Paediatr. 2023 Jul;112(7):1478-1484. doi: 10.1111/apa.16772. Epub 2023 Apr 14.
Impaired resilience to stress may be a factor in sudden infant death syndrome (SIDS). However, no comprehensive studies have been performed on polymorphisms that are relevant to the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the stress hormone cortisol.
We analysed 22 relevant single nucleotide polymorphisms (SNPs) in 206 anonymised SIDS cases who died at a mean of 131 days (range: 5-343) and 256 adult controls who were recruited from paternity testing cases. Additional stratified analyses were performed for sex, age and season of death. Both the cases and the controls were Caucasian.
Variants for rs2235543 (HSD11B1) and rs3779250 (CRHR2) were associated with SIDS in the overall analysis, and borderline for rs2446432 (CRH), at least before corrections for multiple testing. A combination of these three variants was observed in 52.9% of SIDS cases but only 43.0% of controls (p = 0.039). Five or more variants showed an association in the subgroups.
Our findings suggest that the HPA axis influences SIDS and supports the hypothesis that an inadequate stress response may add to the risk. The associated variants for rs2235543, rs3779250 and rs2446432 appeared to decrease the cortisol concentration and impair an appropriate stress response.
压力弹性受损可能是婴儿猝死综合征（SIDS）的一个因素。然而，目前尚未对与调节应激激素皮质醇的下丘脑-垂体-肾上腺（HPA）轴相关的多态性进行全面研究。
我们分析了 206 例匿名 SIDS 病例（死亡时平均年龄为 131 天（范围：5-343））和 256 例成人对照（从亲子鉴定病例中招募）中的 22 个相关单核苷酸多态性（SNP）。还针对性别、年龄和死亡季节进行了分层分析。病例和对照均为白种人。
rs2235543（HSD11B1）和 rs3779250（CRHR2）的变体与整体分析中的 SIDS 相关，rs2446432（CRH）至少在多次检验校正前呈边缘相关。这三种变体的组合在 52.9%的 SIDS 病例中观察到，但在对照组中仅观察到 43.0%（p=0.039）。在亚组中观察到 5 个或更多变体的关联。
我们的研究结果表明，HPA 轴影响 SIDS，并支持应激反应不足可能增加风险的假说。与 rs2235543、rs3779250 和 rs2446432 相关的变体似乎降低了皮质醇浓度并损害了适当的应激反应。
