Genetic predictors of susceptibility to cutaneous fungal infections: a pilot genome wide association study to refine a candidate gene search.
Genetic predictors of susceptibility to cutaneous fungal infections: a pilot genome wide association study to refine a candidate gene search.
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DOI：
10.1016/j.jdermsci.2012.05.003
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发表时间：
2012-08
影响因子：
4.6
通讯作者：
Preuett BL
中科院分区：
文献类型：
--
作者：
Abdel-Rahman SM;Preuett BL
断毛癣菌是美国少数民族儿童最重要的真菌病原体，尽管感染率极高，但这种真菌似乎不会以非特异性方式感染儿童。这项研究旨在确定可能使儿童易患或保护儿童免受T。扁桃体感染参与早期纵向研究的儿童，其中感染率可以可靠地确定有资格入选。来自这些儿童的一个子集（n=40）的DNA在人口极端进行全基因组基因分型（WGG）。病例和对照之间的等位基因频率进行了检查，显着的SNP被用来开发一个候选基因列表，其余的队列（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讨所选基因型预测感染可能性的能力。选择了23个在皮肤感染中具有假定机制作用的基因进行评估。其中，21个基因型之间的感染率存在显着差异。分配给21个基因中的基因型的风险指数占感染率中观察到的变异性的60%以上（校正的r2=0.665，p<0.001）。其中，8似乎解释了观察到的大部分变异性（r2=0.603，p<0.001）。这些基因涉及：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渗透性。将WGG应用于表型极端的个体可以帮助指导在疾病病因学可能是多基因性质的小群体中选择候选基因。
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. This study was designed to identify genes that may predispose or protect a child from T. tonsurans infection. 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. 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 r2=0.665, p<0.001). Among these, 8 appeared to account for the majority of variability that was observed (r2=0.603, p<0.001). These included genes involved in: leukocyte activation and migration, extracellular matrix integrity and remodeling, epidermal maintenance and wound repair, and cutaneous permeability. 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.
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影响因子：
4.5
作者：
Hicks AA;Pramstaller PP;Johansson A;Vitart V;Rudan I;Ugocsai P;Aulchenko Y;Franklin CS;Liebisch G;Erdmann J;Jonasson I;Zorkoltseva IV;Pattaro C;Hayward C;Isaacs A;Hengstenberg C;Campbell S;Gnewuch C;Janssens AC;Kirichenko AV;König IR;Marroni F;Polasek O;Demirkan A;Kolcic I;Schwienbacher C;Igl W;Biloglav Z;Witteman JC;Pichler I;Zaboli G;Axenovich TI;Peters A;Schreiber S;Wichmann HE;Schunkert H;Hastie N;Oostra BA;Wild SH;Meitinger T;Gyllensten U;van Duijn CM;Wilson JF;Wright A;Schmitz G;Campbell H
通讯作者：
Campbell H
影响因子：
8
作者：
Abdel-Rahman, Susan M.;Simon, Steve;Gaedigk, Andrea
通讯作者：
Gaedigk, Andrea
影响因子：
4.4
作者：
Geutskens, Sacha B.;Hordijk, Peter L.;van Hennik, Paula B.
通讯作者：
van Hennik, Paula B.
影响因子：
6.5
作者：
Isard, Olivia;Knol, Anne C.;Dreno, Brigitte
通讯作者：
Dreno, Brigitte
影响因子：
--
作者：
JONES, HE;REINHARDT, JH;RINALDI, MG
通讯作者：
RINALDI, MG