Department of Psychiatry, Social Psychiatry and Psychotherapy, Laboratory for Molecular Neuroscience, Hannover Medical School, Feodor-Lynen-Str. 35, 30625, Hannover, Germany.
Institute of Forensic Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Pediatr Res. 2022 Sep;92(3):694-699. doi: 10.1038/s41390-021-01773-3. Epub 2021 Nov 11.
Based on findings in the brain stems of SIDS victims, the serotonin transporter (5-HTT) gene has been discussed to be associated with SIDS.
In the largest study to date, we investigated the promoter length (5-HTTLPR) and intron 2 VNTR polymorphisms in 274 cases and 264 controls and the Ile425Val polymorphism in 65 cases and 64 controls. Moreover, the methylation of the internal promoter region was investigated in 35 cases and 14 controls.
For 5-HTTLPR, we observed a trend towards an association of allele L (58.8% vs. 53.4%) with SIDS and significant results were observed after stratifying for age, season at death, and prone position. Nevertheless, when pooling all published data, a significant association of allele L with SIDS is confirmed (p: 0.001). For the intron 2 VNTR polymorphism, no significant differences were observed. After pooling, a significant accumulation of the rare allele 9 was observed in SIDS (2.1% vs. 0.6%; p: 0.018). For the Ile425Val polymorphism, no differences were observed.
We conclude that genetic variation at this gene might be of some importance in SIDS. Epigenetic analysis of the internal promoter, however, revealed no influence on the relative risk to succumb to SIDS.
This is the largest study published up to now on 5-HTT gene polymorphisms and SIDS. Polymorphisms in the 5-HTT gene appear to contribute (although to a small degree) to the risk to die from SIDS. There is no evidence that a methylation of the promoter region is of impact for the etiology of SIDS.
基于 SIDS 患者脑干的发现，5-羟色胺转运体（5-HTT）基因已被认为与 SIDS 有关。
在迄今为止最大的研究中，我们调查了 274 例病例和 264 例对照中的启动子长度（5-HTTLPR）和内含子 2VNTR 多态性，以及 65 例病例和 64 例对照中的 Ile425Val 多态性。此外，还研究了 35 例病例和 14 例对照中的内部启动子区域的甲基化情况。
对于 5-HTTLPR，我们观察到等位基因 L（58.8%比 53.4%）与 SIDS 呈趋势相关，并且在按年龄、死亡季节和俯卧位分层后观察到显著结果。然而，当汇总所有已发表的数据时，等位基因 L 与 SIDS 的显著相关性得到证实（p：0.001）。对于内含子 2VNTR 多态性，没有观察到显著差异。汇总后，SIDS 中罕见等位基因 9 的积累显著（2.1%比 0.6%；p：0.018）。对于 Ile425Val 多态性，没有观察到差异。
我们得出结论，该基因的遗传变异可能对 SIDS 有一定的重要性。然而，内部启动子的表观遗传分析并没有显示对死于 SIDS 的相对风险有影响。
这是迄今为止发表的关于 5-HTT 基因多态性和 SIDS 的最大研究。5-HTT 基因的多态性似乎（尽管程度较小）导致死于 SIDS 的风险增加。没有证据表明启动子区域的甲基化对 SIDS 的病因学有影响。
