Department of Pediatric Pulmonology and Immunology, Ghent University Hospital Ghent, Gent, Belgium.
Hum Immunol. 2012 Nov;73(11):1175-83. doi: 10.1016/j.humimm.2012.08.010. Epub 2012 Aug 29.
Genes of innate immunity may be involved in early onset of chronic Pa (Pseudomonas aeruginosa) colonization (cPaC) in cystic fibrosis (CF) patients. We studied 19 single nucleotide polymorphisms (SNPs) in 5 genes coding for proteins of the lectin complement pathway: MBL2 (Mannose binding lectin 2), MASP 1, 2, 3 (MBL-associated serine Protease) and FCN 1, 2 (Ficolin) gene in 96 CF patients. Association survival analysis using different genetic models was performed looking for an association between SNPs and age at onset of cPaC. CF patients who are MBL deficient are earlier chronic Pa colonized compared to MBL sufficient patients. Also patients with MBL2 genotype YO/YO, YO/XA, XA/XA, YA/YO and YA/XA are earlier chronic Pa colonized. CF patients heterozygous or homozygous for mutant alleles of two linked SNPs in the FCN1 gene (rs2989727 and rs1071583) are earlier colonized with Pa. Similarly, earlier onset of Pa colonization is seen in CF patients heterozygous for linked SNPs of FCN2 gene (rs7865453 and rs7851696) and MASP3 gene (rs7851696). Variants in MBL2, FCN1, FCN2 and MASP3 genes are significantly associated with earlier onset of chronic P. aeruginosa colonization.
先天免疫基因可能与囊性纤维化 (CF) 患者慢性铜绿假单胞菌定植 (cPaC) 的早期发病有关。我们研究了编码凝集素补体途径蛋白的 5 个基因中的 19 个单核苷酸多态性 (SNP)：MBL2（甘露聚糖结合凝集素 2）、MASP1、2、3（MBL 相关丝氨酸蛋白酶）和 FCN1、2（ficolin）基因在 96 例 CF 患者中。使用不同的遗传模型进行关联生存分析，以寻找 SNP 与 cPaC 发病年龄之间的关联。与 MBL 充足的患者相比，MBL 缺乏的 CF 患者更早发生慢性 Pa 定植。此外，MBL2 基因型 YO/YO、YO/XA、XA/XA、YA/YO 和 YA/XA 的患者也更早发生慢性 Pa 定植。FCN1 基因（rs2989727 和 rs1071583）两个连锁 SNP 突变等位基因杂合或纯合的 CF 患者更早定植 Pa。同样，CF 患者 FCN2 基因（rs7865453 和 rs7851696）和 MASP3 基因（rs7851696）连锁 SNP 杂合的患者也更早出现 Pa 定植。MBL2、FCN1、FCN2 和 MASP3 基因的变异与慢性铜绿假单胞菌定植的早期发病显著相关。
