A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced nitric oxide production
A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced nitric oxide production
复制标题
DOI：
10.1038/sj.gene.6363909
复制
发表时间：
2002-11-01
影响因子：
5
通讯作者：
Anstey, NM
中科院分区：
文献类型：
--
作者：
Morahan, G;Boutlis, CS;Anstey, NM
白细胞介素-12（IL-12）是一种重要的感染和免疫调节细胞因子。施用IL-12可以减少啮齿动物中严重疟疾的并发症。编码IL-12 p40亚基的基因IL-12 B的多态性影响IL-12的分泌和对1型糖尿病的易感性。因此，我们研究了IL 12 B多态性是否可能影响严重疟疾的结果。IL 12 B启动子多态性的纯合性与坦桑尼亚脑型疟疾儿童死亡率增加相关，但与肯尼亚重症疟疾儿童死亡率无关。此外，IL-12 B启动子多态性的纯合子降低了一氧化氮的产生，这是在垫由IL-12活性调节。这些研究表明，IL-12 B多态性，通过调节IL-12的生产，可能会影响疟疾感染的结果在至少一个非洲人口。
Interleukin-12 (IL-12) is an important regulatory cytokine in infection and immunity. Administration of IL-12 may reduce complications of severe malaria in rodents. Polymorphisms in IL12B, the gene encoding the IL-12 p40 subunit, influence the secretion of IL-12 and susceptibility to Type 1 diabetes. We therefore investigated whether IL12B polymorphisms may affect the outcome of severe malaria. Homozygosity for a polymorphism in the IL12B promoter was associated with increased mortality in Tanzanian children having cerebral malaria but not in Kenyan children with severe malaria. Furthermore, homozygotes for the IL12B promotor polymorphism had decreased production of nitric oxide, which is in pad regulated by IL-12 activity. These studies suggest that IL12B polymorphisms, via regulation of IL-12 production, may influence the outcome of malaria infection in at least one African population.