囊性肺纤维化的加重与MBL2蛋白缺乏有关

Deficiency In The Protein MBL2 Linked To Increased Cystic Fibrosis Severity

ScienceDaily (Feb. 25, 2008) — Cystic fibrosis (CF), a hereditary disorder causing thick mucous production and frequent lung infections, is associated with a high mortality rate primarily due to lung failure.

Although it is known that mutations in the CFTR gene cause the disease, variations in other genes between individuals with CF modify the severity of the disease. For example, the gene responsible for making the MBL2 protein has been suggested to modify lung function in individuals with CF; however, its precise roles in the disease have not been well understood.

In a new study, Julian Zielenski and his colleagues at the Hospital for Sick Children, Toronto, found that genetic variations that modify MBL2 expression were associated with more severe clinical symptoms of CF.

The researchers compared levels of MBL2 in the blood of more than 1,000 CF patients and found that patients deficient in MBL2 were often younger when first infected with the bacteria Pseudomonas aeruginosa, and that their lung function declined more rapidly than patients with normal or high levels of the protein.

These associations between MBL2 and CF severity were even more pronounced in patients that overproduced the protein TGF-beta-1. The authors argue that these findings might provide a basis for new approaches for treating those individuals with CF who are at risk of such increased disease severity.

In an accompanying commentary, Frank Accurso and Marci Sontag at the University of Colorado Denver further suggest that it might be useful to screen for gene variants that cause the production of high levels of MBL2 and TGF-beta-1, as well as other genes that modify the course of CF, in newborn CF screening.

Journal reference: Complex two-gene modulation of lung disease severity in children with cystic fibrosis. Journal of
ScienceDaily（2008-2-25）报道：囊性肺纤维化（CF），一种由浓稠粘液产生和反复肺部感染导致的遗传性异常疾病，具有高死亡率，主要死于肺衰竭。
虽然，囊性纤维跨膜通道调节因子基因（CFTR）突变是这种疾病的病因，但在患有CF的病人之间的不同基因的变异会改变这种疾病的严重度。例如，负责产生MBL2（甘露聚糖结合凝集素）蛋白的基因会改变患CF的病人的肺功能；然而，它在这种疾病中明确的作用还不得而知。
在一项新的研究中，Julian Zielenski和他的同事们对多伦多医院患病儿童进行研究发现：改变MBL2表达的遗传变异与CF临床症状严重度相关。
研究者对比了1000多名CF患者血液中MBL2水平后发现：MBL2缺乏的病人通常是首次感染铜绿假单胞菌时更年轻，而且他们的肺功能下降要比MBL2水平正常或高的病人更快。
MBL2 与CF严重度之间的这些联系，很显然病人过多的产生了转化生长因子β1（TGF-β-1）蛋白。作者指出，这些发现很可能提供一个新的思路去治疗那些具有如此增加疾病严重度风险的CF病人。
在随后的评论中，Colorado Denver 大学的Frank Accurso 和 Marci Sontag指出：与其它改变CF进程的基因同样，引起产生高水平MBL2和 TGF-β-1的基因变异对CF早期病变有很好的屏蔽作用。