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首页> 外文期刊>Journal of dermatological science >Genetic predictors of susceptibility to cutaneous fungal infections: A pilot genome wide association study to refine a candidate gene search
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Genetic predictors of susceptibility to cutaneous fungal infections: A pilot genome wide association study to refine a candidate gene search

机译：皮肤真菌感染易感性的遗传预测因子：一项初步的全基因组关联研究，以完善候选基因搜索

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Background: Trichophyton tonsurans is the foremost fungal pathogen of minority children in the U.S. Despite overwhelming infection rates, it does not appear that this fungus infects children in a non-specific manner. Objective: This study was designed to identify genes that may predispose or protect a child from . T. tonsurans infection. Methods: Children participating in an earlier longitudinal study wherein infection rates could be reliably determined were eligible for inclusion. DNA from a subset (. n=. 40) of these children at the population extremes underwent whole genome genotyping (WGG). Allele frequencies between cases and controls were examined and significant SNPs were used to develop a candidate gene list for which the remainder of the cohort (. n=. 115) were genotyped. Cumulative infection rate was examined by genotype and the ability of selected genotypes to predict the likelihood of infection explored by multivariable analysis. Results: 23 genes with a putative mechanistic role in cutaneous infection were selected for evaluation. Of these, 21 demonstrated significant differences in infection rate between genotypes. A risk index assigned to genotypes in the 21 genes accounted for over 60% of the variability observed in infection rate (adjusted r 2=0.665, p0.001). Among these, 8 appeared to account for the majority of variability that was observed (r 2=0.603, p0.001). These included genes involved in: leukocyte activation and migration, extracellular matrix integrity and remodeling, epidermal maintenance and wound repair, and cutaneous permeability. Conclusions: Applying WGG to individuals at the extremes of phenotype can help to guide the selection of candidate genes in populations of small cohorts where disease etiology is likely polygenic in nature.
机译：背景：扁桃体癣菌是美国少数族裔儿童最重要的真菌病原体。尽管感染率极高，但这种真菌似乎并未以非特异性方式感染儿童。目的：本研究旨在鉴定可能易患儿童或保护其免受感染的基因。扁桃体感染。方法：参加一项较早的纵向研究的儿童有资格被纳入研究，该研究可以可靠地确定感染率。这些儿童的一个子集（.n = .40）在人口极端时的DNA进行了全基因组基因分型（WGG）。检查了病例与对照之间的等位基因频率，并使用了重要的SNPs来建立候选基因列表，对其余队列（.n = .115）进行基因分型。通过基因型检查累积感染率，并通过多变量分析探索所选基因型预测感染可能性的能力。结果：选择了23个在皮肤感染中具有推测的机械作用的基因进行评估。其中，有21个基因型之间的感染率存在显着差异。分配给21个基因的基因型的风险指数占感染率变化的60％以上（调整后r 2 = 0.665，p <0.001）。在这些变量中，有8个似乎是观察到的大多数变异的原因（r 2 = 0.603，p <0.001）。这些基因包括：白细胞活化和迁移，细胞外基质完整性和重塑，表皮维持和伤口修复以及皮肤通透性。结论：将WGG应用于表型极端的个体可以帮助指导在病因学上可能是多基因的小队列人群中选择候选基因。

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