Infectious Diseases, Genome Institute of Singapore, Singapore.
Nat Genet. 2010 Sep;42(9):772-6. doi: 10.1038/ng.640. Epub 2010 Aug 8.
Meningococcal disease is an infection caused by Neisseria meningitidis. Genetic factors contribute to host susceptibility and progression to disease, but the genes responsible for disease development are largely unknown. We report here a genome-wide association study for host susceptibility to meningococcal disease using 475 individuals with meningococcal disease (cases) and 4,703 population controls from the UK. We performed, in Western European and South European cohorts (consisting of 968 cases and 1,376 controls), two replication studies for the most significant SNPs. A cluster of complement factor SNPs replicated independently in both cohorts, including SNPs within complement factor H (CFH) (rs1065489 (p.936D<E), P = 2.2 x 10(-11)) and in CFH-related protein 3 (CFHR3)(rs426736, P = 4.6 x 10(-13)). N. meningitidis is known to evade complement-mediated killing by the binding of host CFH to the meningococcal factor H-binding protein (fHbp). Our study suggests that host genetic variation in these regulators of complement activation plays a role in determining the occurrence of invasive disease versus asymptomatic colonization by this pathogen.
脑膜炎球菌病是由脑膜炎奈瑟菌引起的感染。遗传因素导致宿主易感性和疾病进展，但导致疾病发展的基因在很大程度上尚不清楚。我们在此报告了一项使用英国的 475 名脑膜炎球菌病患者（病例）和 4703 名人群对照进行的脑膜炎球菌病宿主易感性的全基因组关联研究。我们在西欧和南欧队列（包括 968 例病例和 1376 例对照）中对最显著的 SNP 进行了两项复制研究。一组补体因子 SNP 在两个队列中独立复制，包括补体因子 H（CFH）内的 SNP（rs1065489（p.936D<E），P=2.2x10(-11)) 和 CFH 相关蛋白 3（CFHR3）（rs426736，P=4.6x10(-13)）。众所周知，脑膜炎奈瑟菌通过宿主 CFH 与脑膜炎奈瑟菌因子 H 结合蛋白（fHbp）结合来逃避补体介导的杀伤。我们的研究表明，这些补体激活调节剂中的宿主遗传变异在决定该病原体引起侵袭性疾病与无症状定植方面发挥作用。
