Background

YKL-40 (chitinase 3-like 1 gene; CHI3L1) is an inflammatory marker that is increased in the blood of patients with inflammatory diseases, including cystic fibrosis (CF). The objective of our study was to explore the relationship between circulating levels of YKL-40, selected CHI3L1 single nucleotide polymorphisms (SNPs) and the severity of CF disease.

Methods

A prospective cohort of 188 adult patients with CF was established in 2015. Blood samples and clinical data were collected over 2 years to analyze the circulating levels of YKL-40 and to genotype selected CHI3L1 SNPs. We also looked for an association between these factors and clinical parameters.

Results

We found that according to the serum YKL-40 concentration, the patients could be categorized into two distinct groups: low and high YKL-40. Compared to the patients in the low YKL-40 group, the patients in the high YKL-40 group had lower lung function (P < 0.001), a higher proportion of delF508 homozygote mutations (P= 0.027) and dysglycemia (P= 0.015). They were also more colonized with Pseudomonas aeruginosa (P= 0.003) and required more frequent antibiotic intravenous courses (P < 0.001). We also observed that patients expressing the C/C-rs4950928 genotype had higher levels of YKL-40 in their blood and were more frequently dysglycemic.

Conclusion

Our study suggests that YKL-40 could be a potential biomarker of CF disease severity. Furthermore, the CHI3L1 rs4950928 SNP could be a susceptible gene that could be used by CF health professionals to identify patients who are the most at risk of having a severe clinical profile.

中文翻译：

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YKL-40 作为成人 CF 患者的临床生物标志物：CHI3L1 单核苷酸多态性对疾病严重程度的影响

背景

YKL-40（几丁质酶 3 样 1 基因；CHI3L1）是一种炎症标志物，在包括囊性纤维化 (CF) 在内的炎症性疾病患者的血液中升高。我们研究的目的是探讨 YKL-40 的循环水平、选定的 CHI3L1 单核苷酸多态性 (SNP) 与 CF 疾病严重程度之间的关系。

方法

2015 年建立了 188 名成年 CF 患者的前瞻性队列。收集了 2 年多的血液样本和临床数据，以分析 YKL-40 的循环水平并对选定的 CHI3L1 SNP 进行基因分型。我们还寻找这些因素与临床参数之间的关联。

结果

我们发现，根据血清 YKL-40 浓度，患者可分为两组：低 YKL-40 和高 YKL-40。与低 YKL-40 组患者相比，高 YKL-40 组患者肺功能较低（P < 0.001）、delF508 纯合突变比例较高（P = 0.027）和血糖异常（P = 0.015） . 他们也更多地被铜绿假单胞菌定植（P = 0.003），并且需要更频繁的抗生素静脉注射疗程（P < 0.001）。我们还观察到表达 C/C-rs4950928 基因型的患者血液中的 YKL-40 水平较高，并且更频繁地出现血糖异常。

结论

我们的研究表明，YKL-40 可能是 CF 疾病严重程度的潜在生物标志物。此外，CHI3L1 rs4950928 SNP 可能是一种易感基因，CF 卫生专业人员可以使用该基因来识别最有可能出现严重临床特征的患者。