贵州汉族慢性阻塞性肺疾病患者Toll样受体1基因多态性与肺念珠菌感染及定植的相关性

Association of TLR1 gene polymorphisms with pulmonary candida infection and candida colonization in Guizhou Han patients with chronic obstructive pulmonary disease

目的 Toll样受体(TLRs)基因多态性与中国汉族人群真菌感染的相关性研究鲜有报道。文中探讨贵州汉族人群TLRs基因单核苷酸多态性(SNP)与慢性阻塞性肺疾病(COPD)患者肺念珠菌感染及定植的相关性。方法采用聚合酶链反应-直接测序分型(PCR-SBT)法检测344例COPD汉族患者TLR1、2和4基因6个SNP位点的基因型。其中80例合并肺念珠菌感染(肺念珠菌感染组),103例合并念珠菌定植(念珠菌定植组),161例为阴性对照(对照组)。SNPstats在线软件分析在不同遗传模式下单个SNP与COPD患者肺念珠菌感染、念珠菌定植的相关性。采用酶联免疫吸附实验(ELISA)检测肺念珠菌感染者血浆中IL-6、IL-8、IL-1β及TNF-α蛋白水平,评估多态性的功能性结果。结果所有样本均未检测到rs5743611、rs5743708、rs4986790及rs4986791的多态性。rs4833095位点在共显性、显性与超显性遗传模式下肺念珠菌感染组与对照组间基因型的分布差异有统计学意义(P<0.05),显性遗传模型是该位点最佳遗传模式。念珠菌定植组与对照组间rs4833095基因型分布差异无统计学意义(P>0.05)。rs5743618基因型分布在所有组间差异均无统计学意义(P均>0.05)。肺念珠菌感染组rs4833095的T等位基因能降低血浆中IL-6、IL-8、IL-1β水平,差异有统计学意义(P<0.05)。该位点的T等位基因降低血浆中TNF-α水平,差异无统计学意义(P>0.05)。结论 TLR1基因rs4833095多态性与慢性阻塞性肺疾病患者肺念珠菌感染的易感性有关。该位点的T等位基因可能影响TLR1的功能,降低血浆中IL-6、IL-8、IL-1β蛋白水平。rs4833095与rs5743618多态性与念珠菌定植易感无关。

Objective Studies are rarely reported on the correlation of the Toll-like receptor(TLR)gene polymorphisms with fungal infection in the Chinese Han population.This study aims to explore the association between TLR gene polymorphisms and pulmonary candida infection(PCI)and candida colonization(CC)in patients with chronic obstructive pulmonary disease(COPD)in the Guizhou Han population.Methods Using the polymerase chain reaction-direct sequencing(PCR-SBT)method,we genotyped six single nucleotide polymorphisms(SNP)of the TLR1,TLR2 and TLR4 genes in 344 Guizhou Han patients with COPD,including 80 cases complicated by PCI(the PCI group),103 cases complicated correlation of the SNPs with PCI and CC in the COPD patients in different genetic models with the SNPstats online software,measured the levels of IL-6,IL-8,IL-1βand TNF-αproteins in the plasma of the patients by ELISA,and assessed the functional consequences of these polymorphisms.Results The polymorphisms of rs5743611,rs5743708,rs4986790 and rs4986791 were found in none of the patients.The genotype frequency of rs4833095 was significantly different between the PCI and control groups in the codominant,dominant and overdominant models(P<0.05),with the dominant model as the best genetic pattern.No statistically significant differ-ence was observed either in the rs4833095 genotype frequency between the CC and control groups(P>0.05)or in the rs5743618 genotype frequency between any two groups(P>0.05).In the PCI group,the T allele of the rs4833095 polymorphism significantly decreased the levels of IL-6,IL-8 and IL-1βin the plasma(P<0.05),and that of TNF-αas well,though with no statistically significant difference(P>0.05).Conclusion The rs4833095 polymorphism of the TLR1 gene is associated with PCI in COPD patients.The T allele of rs4833095 may affect the function of TLR1,decrease the levels of IL-6,IL-8 and IL-1βproteins in the plasma.Neither rs4833095 nor rs5743618 gene polymorphism is correlated with the susceptibility to candida colonization.