The Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, Massachusetts.
Am J Trop Med Hyg. 2021 Sep 27;105(6):1706-1711. doi: 10.4269/ajtmh.20-0617.
In low-resource settings, Cryptosporidium spp. is a common cause of diarrheal disease in children under the age of 3 years. In addition to diarrhea, these children also experience subclinical episodes that have been shown to affect growth and cognitive function. In this study, we screened polymorphisms in the promoter and exon1 regions of the mannose binding lectin 2 (MBL2) gene, as well as single nucleotide polymorphisms (SNPs) described in toll-like receptors (TLR) TLR1, TLR2, TLR4, and TLR9 and TIR domain-containing adaptor protein (TIRAP) genes among children with cryptosporidial diarrhea (cases) and children who only experienced asymptomatic (subclinical) cryptosporidiosis (controls). Among the polymorphisms screened, the variant allele B at codon 54 (rs1800450) of the MBL2 gene was associated with susceptibility to cryptosporidial diarrhea (odds ratio [OR] = 2.2, 95% confidence interval [CI] 1.1-4.5). When plasma MBL levels were compared, 72% of cases were found to be deficient compared with 32% among controls (OR = 5.09). Among TLR polymorphisms screened, multivariate analysis showed that heterozygous genotypes of TLR4 896A/G (rs4986790, OR = 0.33, 95% CI: 0.11-0.98) and TIRAP 539 C/T (rs8177374, OR = 0.19, 95% CI: 0.06-0.64) SNPs were associated with protection from cryptosporidial diarrhea. Although not statistically significant, these findings suggest that polymorphisms of MBL2 and TLR genes influence susceptibility to symptomatic cryptosporidial diarrhea even in settings with high exposure levels. Further studies to validate these findings in a larger cohort and to understand the role of these polymorphisms in mediating innate and adaptive immune responses to cryptosporidial infection are necessary.
在资源匮乏的环境中，隐孢子虫属是 3 岁以下儿童腹泻病的常见病因。除了腹泻，这些儿童还会出现亚临床症状，这些症状已被证明会影响生长和认知功能。在这项研究中，我们筛选了甘露聚糖结合凝集素 2（MBL2）基因启动子和外显子 1 区的多态性，以及 Toll 样受体（TLR）TLR1、TLR2、TLR4 和 TLR9 和 TIR 结构域包含衔接蛋白（TIRAP）基因中的单核苷酸多态性（SNP），这些基因存在于患有隐孢子虫性腹泻（病例）的儿童和仅患有无症状（亚临床）隐孢子虫病（对照）的儿童中。在所筛选的多态性中，MBL2 基因密码子 54 处的变异等位基因 B（rs1800450）与隐孢子虫性腹泻易感性相关（比值比 [OR] = 2.2，95%置信区间 [CI] 1.1-4.5）。当比较血浆 MBL 水平时，发现 72%的病例存在缺乏，而对照中只有 32%（OR = 5.09）。在所筛选的 TLR 多态性中，多变量分析显示 TLR4 896A/G（rs4986790）杂合基因型（OR = 0.33，95%CI：0.11-0.98）和 TIRAP 539 C/T（rs8177374）与隐孢子虫性腹泻的保护相关（OR = 0.19，95%CI：0.06-0.64）。尽管没有统计学意义，但这些发现表明 MBL2 和 TLR 基因的多态性影响对有症状的隐孢子虫性腹泻的易感性，即使在高暴露水平的环境中也是如此。需要进一步的研究来验证这些发现，并在更大的队列中了解这些多态性在介导对隐孢子虫感染的先天和适应性免疫反应中的作用。
