摘要目的 通过病例-对照关联研究,探讨β-防御素1(DEFB1)基因多态性与重症脓毒症患者真菌感染易感性的相关性.方法 依据1992年和2002年美国胸科医师协会/美国危重病学会(ACCM/SCCM)制订的重症脓毒症诊断标准,将ICU中符合重症脓毒症诊断标准的211例患者纳入研究,并根据在ICU期间是否发生真菌感染将其进一步分为真菌感染组和对照组.通过DNA直接测序、聚合酶联反应双引物等位基因特异性扩增法(PCR-ASA)或Taqman方法检测DEFB1基因-1816A/G、-390A/T、-52A/G、-44C/G、-20A/G等5位点在两组患者中的等位基因和基因型,用遗传分析法计算其单倍型的分布频率,采用x2检验或Fisher精确概率法分析这些遗传变异与重症脓毒症患者真菌感染易感性的相关性,并以相对风险度(odds ratio,OR)反映该遗传因素与其关联的程度. 结果真菌感染组共纳入80例患者,对照组为131例.真菌感染组中男性43例(53.8%),年龄(60.81±18.30)岁;对照组男性80例(6J.1%),年龄(60.42±17.03)岁,两组间性别组成、平均年龄差异无统计学意义(P＞0.05).DEFB1基因-1816A/G、-390A/T、-52A/G、-44C/G和-20A/G位点在两组人群中都遵守Hardy-Weinberg平衡,其基因型分布和等位基因频率在真菌感染组和对照组之间差异均无统计学意义(P＞0.05).上述5个位点的常见单倍型AAACG、ATGCA、GTGGG和ATACG在真菌感染组和对照组之间的分布频率差异均无统计学意义(P＞0.05). 结论 DEFB1基因-1816A/G、-390A/T、-52A/G、-44C/G和-20A/G位点与重症脓毒症患者真菌感染的发生不相关,提示DEFB1基因遗传变异可能不是重症脓毒症患者真菌易感性的重要遗传学位点.

abstractsObjective To investigate the correlation between gene polymorphism within human β defensin 1 (DEFB1) and fungal susceptibility to severe sepsis through case-control association study.Methods A total of211 patients with severe sepsis in ICU were enrolled in the present case control study. Sepsis in this study was diagnosed according to the definition of American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference in 1992 and 2002. Based on the development of fungal infection during ICU stay, all 211 patients were divided into fungal infection group (Group Ⅰ) and control group (Group C). Alleles and genotypes of-1816A/G, -390A/T, -52A/G, -44C/G and-20A/G within DEFB1 gene were assayed in all 211 patients by means of DNA direct sequencing, Allele-specific PCR amplifications or high-throughput site-specific TaqMan assay. Genetic analysis was employed to calculate the distribution frequency of haplotypes. The correlation between the genomic variations (allele,genotype and haplotype) and fungal infection was analyzed by Chi-square test or Fisher's exact test.Odds ratio (OR) was employed to reflect the correlation degree of genetic factor with fungal susceptibility to severe sepsis. Results Group Ⅰ enrolled 80 patients, of whom 43 pstients were male, at age of (60.81 ± 18.30) years. Group C enrolled 131 patients, of whom 80 patients were male, at mean age of (60.42 ± 17.03) years. No significant difference was found between two groups in aspect of gender and age (P＞0.05). The genetic locus of -1816A/G, -390A/T, -52A/G, -44C/G and -20A/G of both groups were in agreement with Hardy Weinberg equilibrium. No significant difference was found between two groups in the distribution of allelic frequencies and genotype frequencies (P ＞0.05). No significant difference was found in the distribution frequency of four common haplotypes of the above five genetic locus such as AAACG, ATGCA, GTGGG and ATACG (all P ＞ 0.05). Conclusions Genetic locus of -1816A/G, -390A/T, -52A/G, -44C/G and-20A/G within DEFB1 gene have no correction with fungal infections in severe sepsis, suggesting that DEFB1 gene polymorphism may not serve as a key genetic marker for the predisposition to fungal infection in severe sepsis.