Molecularr epidemiology about unexpected sudden death

我们已经建立了三个基因组库。第一个基因组库由近1000名日本人组成，主要来自高血压病例对照研究的诊所。第二银行是由来自日本各地农村的21000名日本普通人口组成的。第三岸由近1000名蒙古人组成。利用高血压病例对照基因组面板，研究人员发现先天免疫相关基因冷自身炎症综合征1 （CIAS1, NLRP3）的子内可变数串联重复序列多态性存在关联。重复数与外周白细胞的转录水平相关。高表达基因型患者血压高于低表达基因型患者。CIAS1表达水平与白细胞介素-1表达水平相关(3)。在成年转基因小鼠体内注射低剂量脂多糖后，白细胞中表达人CIAS1的转基因小鼠易发生新生儿重症肺炎和无菌性肺炎死亡。腹腔巨噬细胞胞质中pre-IL-113的表达增强，细胞外11l -1β的分泌增强，提示先天免疫分子的表达水平可能通过增强炎症反应参与高血压的易感性。胰岛素抵抗是动脉硬化性疾病的主要发病机制之一。采用蒙古糖尿病病例对照组调查新近鉴定的脂肪因子与视黄醇结合蛋白的相关性。4 (RBP4)。与一个调节SNP有显著关联，该SNP的一个小等位基因增强了肝细胞和脂肪细胞的表达。RBP4调节SNP也与日本人的BMI相关。来自脂肪细胞的RBP4可能参与脂肪形成和进一步的胰岛素抵抗。这些基于群体遗传学的研究发现了几个与常见疾病相关的新位点。这些遗传因素是否涉及法医案件仍有待评估。少

We have constructed three genome banks. The first genome bank is consisted with almost 1000 Japanese population mainly collected from clinics for hypertension case-control study. The second bank is consisted with 21000 Japanese general population from rural area of all over Japan. The third bank is consisted with almost 1000 Mongolian population.Using the hypertension case-control genome panel, we found an association of an intronic variable number of tandem repeat polymorphism in an innate immunity associated gene, that is Cold autoinflammatory syndrome 1 (CIAS1, NLRP3). The repeat number correlated with the transcript level in peripheral leukocytes. The high expresser genotype showed higher blood pressure than the low expresser type, and the. CIAS1 expression level correlated with expression of interleukin-1 (3. The transgenic mice expressing human CIAS1 in leukocytes were susceptible to newborn death from severe pneumonitis and aseptic pneumonitis after injection of low dose lipopol … More ysaccharide into adult transgenic mice. The peritoneal -macrophages showed enhanced expression of pre-IL-113 in the cytoplasm and enhanced the extracellular excretion of 1L-1β These data implicated that the expression level of the molecule of innate immunity may be involved in the susceptibility of hypertension through the enhanced inflammatory response.Insulin resistance is one of the principal pathogenesis of arteriosclerotic disorders. Mongolian diabetic case-control panel was used to survey the association of recently identified adipokine, retinol binding protein. 4 (RBP4). A significant association was shown with a regulatory SNP, minor allele of which enhanced the expression in both hepatocytes and adipocytes. The RBP4 regulatory SNP was also correlated with BMI in Japanese. RBP4 from adipocytes may be involved in the adipogenesis and further insulin resistance.These population genetics based studies identified several novel loci associated with common diseases. Whether these genetic factors are involved in the forensic cases remains to be assessed. Less