Association of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease
Association of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease
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DOI：
10.1016/s0140-6736(98)08350-0
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发表时间：
1999-03-27
期刊：
影响因子：
168.9
通讯作者：
Levin, M
中科院分区：
文献类型：
--
作者：
Hibberd, ML;Sumiya, M;Levin, M
背景脑膜炎球菌病只在一小部分携带致病细菌的个体中发生的原因尚不清楚。宿主对细菌定植的反应差异被认为是相关的，因为补体途径或备解素末端成分缺乏的人容易患脑膜炎球菌病。我们假设，遗传变异的甘露糖结合凝集素（MBL），血浆调理素，启动另一条途径的补体激活，可能同样会导致易感性脑膜炎球菌diseases.Methods的频率变异的MBL基因被确定在儿童与脑膜炎球菌疾病和控制从两个独立的研究;一家医院（194例患者和272例对照[非感染性疾病患者]），以及一项基于社区的（72名患者和110名对照[健康个体]），通过PCR和限制性酶切，结果在医院研究中，脑膜炎球菌病患者MBL变异等位基因纯合子的比例高于对照组，（15 [7.7%] vs 4 [1.5%];比值比6.5 [95%CI 2.0-27.2]）和社区研究（6 [8.3%] vs 3 [2.7%]; 4.5 [0.9-29.1]）。MBL变异（纯合子和杂合子）病例的人群归因分数为32%。解释MBL途径是脑膜炎球菌病易感性的关键决定因素，MBL的遗传变异可能占所有疾病病例的三分之一。
Background The reasons why meningococcal disease develops in only a small proportion of individuals carrying the causative bacteria are unknown. Differences in host responses to bacterial colonisation are thought to be involved, since people with deficiencies in the terminal components of the complement pathway, or of properdin, are susceptible to meningococcal disease. We postulate that genetic variants of mannose-binding lectin (MBL), a plasma opsonin that initiates another pathway of complement activation, might similarly cause susceptibility to meningococcal disease.Methods The frequency of variants of the MBL gene was ascertained in children with meningococcal disease and controls from two independent studies; one hospital-based (194 patients and 272 controls [patients with noninfectious disorders]), and one community-based (72 patients and 110 controls [healthy individuals]), by means of PCR and restriction-enzyme digestion, with confirmation by DNA sequencing.Findings The proportion of people homozygous for MBL-variant alleles was higher in patients with meningococcal disease than in controls in the hospital study (15 [7.7%] vs four [1.5%]; odds ratio 6.5 [95% CI 2.0-27.2]) and in the community study (six [8.3%] vs three [2.7%]; 4.5 [0.9-29.1]). The population attributable fraction of cases attributable to MBL variants (homozygous and heterozygous) was 32%,Interpretation The MBL pathway is a critical determinant of meningococcal-disease susceptibility, and genetic variants of MBL might account for a third of all disease cases.