Adhesion between the opacity-associated adhesin (Opa) proteins of Neisseria meningitidis and human carcino-embryonic antigen cell adhesion molecule (CEACAM) proteins is an important stage in the pathogenesis of meningococcal disease, a globally important bacterial infection. Most disease is caused by a small number of meningococcal genotypes known as hyperinvasive lineages. As these are also carried asymptomatically, acquisition of them alone cannot explain why only some hosts develop meningococcal disease. Our aim was to determine whether genetic diversity in CEACAM is associated with susceptibility to meningococcal disease. Frequency distributions of alleles, genotypes and haplotypes were compared in four CEACAM genes in 384 case samples and 190 controls. Linkage disequilibrium among polymorphic sites, haplotype structures and relationships were also analysed. A number of polymorphisms were observed in CEACAM genes but the diversity of CEACAM1, to which most Opa proteins bind, was lower, and a small number of high-frequency haplotypes were detected. Dose-dependent associations of three CEACAM haplotypes with meningococcal disease were observed, with the effect of carrying these haplotypes amplified in homozygous individuals. Two haplotypes were protective while one haplotype in CEACAM6 was associated with a twofold increase in disease susceptibility. These data imply that human CEACAM may be one determinant of human susceptibility to meningococcal disease.

中文翻译：

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人类 CEACAM 基因的单倍型多样性：对脑膜炎球菌病易感性的影响。

脑膜炎奈瑟菌的混浊相关粘附素 (Opa) 蛋白与人类癌胚抗原细胞粘附分子 (CEACAM) 蛋白之间的粘附是脑膜炎球菌疾病发病机制中的一个重要阶段，这是一种全球重要的细菌感染。大多数疾病是由少数称为超侵袭性谱系的脑膜炎球菌基因型引起的。由于这些也是无症状携带的，仅获得它们并不能解释为什么只有一些宿主会患上脑膜炎球菌病。我们的目的是确定 CEACAM 的遗传多样性是否与脑膜炎球菌病的易感性有关。比较了 384 个病例样本和 190 个对照中四个 CEACAM 基因的等位基因、基因型和单倍型的频率分布。多态位点之间的连锁不平衡，还分析了单倍型结构和关系。在 CEACAM 基因中观察到许多多态性，但大多数 Opa 蛋白结合的 CEACAM1 的多样性较低，并且检测到少量高频单倍型。观察到三种 CEACAM 单倍型与脑膜炎球菌疾病的剂量依赖性关联，携带这些单倍型的效果在纯合个体中被放大。两种单倍型具有保护作用，而 CEACAM6 中的一种单倍型与疾病易感性的两倍增加相关。这些数据暗示人类 CEACAM 可能是人类对脑膜炎球菌病易感性的决定因素之一。并检测到少量高频单倍型。观察到三种 CEACAM 单倍型与脑膜炎球菌疾病的剂量依赖性关联，携带这些单倍型的效果在纯合个体中被放大。两种单倍型具有保护作用，而 CEACAM6 中的一种单倍型与疾病易感性的两倍增加相关。这些数据暗示人类 CEACAM 可能是人类对脑膜炎球菌病易感性的决定因素之一。并检测到少量高频单倍型。观察到三种 CEACAM 单倍型与脑膜炎球菌疾病的剂量依赖性关联，携带这些单倍型的效果在纯合个体中被放大。两种单倍型具有保护作用，而 CEACAM6 中的一种单倍型与疾病易感性的两倍增加相关。这些数据暗示人类 CEACAM 可能是人类对脑膜炎球菌病易感性的决定因素之一。