Fard Delnaz, Läer Katharina, Rothämel Thomas, Schürmann Peter, Arnold Matthias, Cohen Marta, Vennemann Mechtild, Pfeiffer Heidi, Bajanowski Thomas, Pfeufer Arne, Dörk Thilo, Klintschar Michael
Institute of Legal Medicine, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany.
Gynaecology Research Unit, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany.
Int J Legal Med. 2016 Jul;130(4):1025-1033. doi: 10.1007/s00414-016-1347-y. Epub 2016 Mar 14.
Sudden infant death syndrome (SIDS) causes early infant death with an incidence between 0.5 and 2.5 cases among 1000 live births. Besides central sleep apnea and thermal dysregulation, infections have been repeatedly suggested to be implicated in SIDS etiology.
To test the risk contribution of common genetic variants related to infection, we genotyped 40 single-nucleotide polymorphisms (SNPs) from 15 candidate genes for association with SIDS in a total of 579 cases and 1124 controls from Germany and the UK in a two-stage case control design.
The discovery-stage series (267 SIDS cases and 303 controls) revealed nominally significant associations for variants in interleukin 6 (IL6) (rs1880243), interleukin 10 (IL10) (rs1800871, rs1800872), and mannose-binding lectin 2 (MBL2) (rs930506), and for several other variants in subgroups. Meta-analyses were then performed in adding genotype information from a genome-wide association study of another 312 European SIDS cases and 821 controls. Overall associations were observed for two independent variants in MBL2: rs930506 in a co-dominant model (odds ratio (OR) = 0.82, p = 0.04) and rs1838065 in a dominant model (OR = 1.27, p = 0.03).
Our study did not replicate published associations of IL10 variants with SIDS. 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.
婴儿猝死综合征（SIDS）导致婴儿早期死亡，在1000例活产中发病率为0.5至2.5例。除了中枢性睡眠呼吸暂停和体温调节异常外，感染一再被认为与SIDS病因有关。
为了测试与感染相关的常见基因变异的风险贡献，我们在德国和英国的579例病例和1124例对照中，采用两阶段病例对照设计，对15个候选基因的40个单核苷酸多态性（SNP）进行基因分型，以确定其与SIDS的关联。
发现阶段系列（267例SIDS病例和303例对照）显示，白细胞介素6（IL6）（rs1880243）、白细胞介素10（IL10）（rs1800871、rs1800872）和甘露糖结合凝集素2（MBL2）（rs930506）中的变异以及亚组中的其他几个变异存在名义上的显著关联。然后，在纳入另外312例欧洲SIDS病例和821例对照的全基因组关联研究的基因型信息后进行荟萃分析。在MBL2中观察到两个独立变异的总体关联：共显性模型中的rs930506（优势比（OR）=0.82，p=0.04）和显性模型中的rs1838065（OR=1.27，p=0.03）。
我们的研究没有重复已发表的IL10变异与SIDS的关联。然而，在两个大型系列的联合分析中，两个独立的MBL2变异的证据似乎与感染可能在SIDS发病机制中起作用的假设一致。
