Single-nucleotide Polymorphisms (SNPs) in human β-defensin 1:: High-throughput SNP assays and association with Candida carriage in type I diabetics and nondiabetic controls
Single-nucleotide Polymorphisms (SNPs) in human β-defensin 1:: High-throughput SNP assays and association with Candida carriage in type I diabetics and nondiabetic controls
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DOI：
10.1128/jcm.41.1.90-96.2003
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发表时间：
2003-01-01
影响因子：
9.4
通讯作者：
Dale, BA
中科院分区：
文献类型：
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作者：
Jurevic, RJ;Bai, M;Dale, BA
β-防御素是在上皮细胞中表达的阳离子抗微生物肽。它们具有抗菌、抗真菌和抗病毒特性。防御素是先天免疫反应的一个组成部分，并且已经提出它们在口腔中具有保护作用。先前的研究表明，人β-防御素1（hBD-1）在口腔上皮细胞中组成型表达，但表达在个体之间存在差异。我们检验了防御素肽表达的遗传变异可能与机会性感染相关的假设。这在免疫功能低下的患者群体中可能是至关重要的，其中先天免疫应答可能具有相对更重要的作用。在I型糖尿病患者（n = 43）和非糖尿病对照组（n = 50）中评估口腔念珠菌携带状态和编码hBD-1的DEFB 1基因中存在的6个单核苷酸多态性（SNP）。从口腔拭子获得基因组DNA。扩增DEFB 1基因的部分，并通过TaqMan测定分析每个SNP，用已知基因型的对照DNA标准化。在CHROMagar平板培养基上从未刺激的唾液确定念珠菌携带状态。低水平的念珠菌携带定义为小于或等于350 CFU/ml。44%的糖尿病患者念珠菌携带率较高，而非糖尿病对照组仅为28%（P < 0.05）。C.白色念珠菌占优势;然而，糖尿病受试者，尤其是携带水平高的受试者，光滑念珠菌和念珠菌的比例增加。热带植物在两组中，5'非翻译区的SNP（位置-44处的C->G）与念珠菌携带之间存在强关联。在具有SNP等位基因2（G）的糖尿病人群中，58%具有低CFU，而6%具有高CFU。位置-44处的C->G SNP与低水平的念珠菌携带相关。所得比值比对于保护作用具有统计学显著性（糖尿病受试者的比值比为25，非糖尿病受试者为8.5）。这些结果表明，编码hBD-1的DEFB 1基因的遗传变异可能在介导和/或促进口腔感染的易感性方面发挥重要作用。
beta-Defensins are cationic antimicrobial peptides expressed in epithelia. They exhibit antibacterial, antifungal, and antiviral properties. Defensins are a component of the innate immune response, and it has been proposed that they have a protective role in the oral cavity. Previous studies have shown that human beta-defensin 1 (hBD-1) is constitutively expressed in oral epithelial cells but that expression varies between individuals. We tested the hypothesis that genetic variations in defensin peptide expression may be associated with opportunistic infections. This may be critical in the immunocompromised patient population, in which innate immune responses may have a relatively more important role. Oral Candida carriage status and the presence of six single-nucleotide polymorphisms (SNPs) in the DEFB1 gene encoding hBD-1 were evaluated in type I diabetic patients (n = 43) and nondiabetic controls (n = 50). Genomic DNA was obtained from buccal swabs. Portions of the DEFB1 gene were amplified, and each SNP was analyzed by a TaqMan assay, standardized with control DNA of known genotype. Candida carriage status was determined from unstimulated saliva on CHROMagar plating medium. A low level of Candida carriage was defined as less than or equal to350 CFU/ml. A high level of Candida carriage was seen in 44% of the diabetic subjects but only in 28% of the nondiabetic controls (P < 0.05). C. albicans predominated; however, diabetic subjects, especially those with high levels of carriage, showed an increased proportion of Candida glabrata and C. tropicalis. There was a strong association between an SNP in the 5' untranslated region (C-->G at position -44) and Candida carriage in both groups. Among individuals in the diabetic population who had the SNP allele 2 (G), 58% had low CFU, while 6% had high CFU. The C-->G SNP at position -44 is associated with low levels of Candida carriage. The resultant odd ratios are statistically significant for a protective effect (odd ratios, 25 for diabetic subjects and 8.5 for nondiabetic subjects). These results indicate that genetic variations in the DEFB1 gene encoding hBD-1 may have a major role in mediating and/or contributing to susceptibility to oral infection.