MUC1 gene polymorphisms are associated with serum KL-6 levels and pulmonary dysfunction in pulmonary alveolar proteinosis.
MUC1 gene polymorphisms are associated with serum KL-6 levels and pulmonary dysfunction in pulmonary alveolar proteinosis.
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DOI：
10.1186/s13023-016-0430-2
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发表时间：
2016-04-23
影响因子：
3.7
通讯作者：
Costabel U
中科院分区：
文献类型：
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作者：
Bonella F;Long X;Ohshimo S;Horimasu Y;Griese M;Guzman J;Kohno N;Costabel U
KL-6是一种人MUC1粘蛋白，是肺间质性疾病（包括肺泡蛋白沉积症（PAP））的敏感生物标志物。MUC1基因单核苷酸多态性（SNP） rs4072037基因型与血清KL-6水平存在相关性。本研究旨在探讨PAP患者MUC1 SNP基因型与疾病严重程度及疾病转归的相关性。研究对象为24例PAP患者和30名健康志愿者。采用实时聚合酶链反应（RT-PCR）检测MUC1 rs4072037。采用焦磷酸测序进行基因分型。采用Nanopia KL-6测定法（SEKISUI Diagnostics）测定血清中KL-6水平。PAP患者与健康志愿者MUC1 rs4072037等位基因频率差异有统计学意义（PAP, A/A 46%, A/G 54%, G/G 0%；健康对照组，A/A 30%, A/G 40%, G/G 30%; p = 0.013）。PAP患者血清KL-6水平显著高于对照组（p < 0.0001）， A/A基因型PAP患者血清KL-6水平显著高于A/G基因型PAP患者血清KL-6水平（p = 0.007）。与A/G基因型患者相比，A/A基因型患者肺泡动脉氧差（A- ado2）较高，DLco较低（p = 0.027和p = 0.012）。多因素分析、Kaplan-Meier分析和C统计显示，rs4072037 A/A基因型与较高的疾病进展率相关（HR: 5.557, p = 0.014）。MUC1 rs4072037 A/A基因型与PAP患者更严重的肺功能障碍和更高的疾病进展率相关。
KL-6, a human MUC1 mucin, is a sensitive biomarker for interstitial lung diseases including pulmonary alveolar proteinosis (PAP). A correlation between MUC1 gene single nucleotide polymorphism (SNP) rs4072037 genotype and serum KL-6 levels has been reported. This study was aimed at investigating the correlation between MUC1 SNP genotype, severity of disease and disease outcome in PAP. Twenty four patients with PAP and 30 healthy volunteers were studied. MUC1 rs4072037 was detected by using a real-time polymerase chain reaction (RT-PCR). Genotyping was performed by pyrosequencing. KL-6 levels were measured in serum by Nanopia KL-6 assay (SEKISUI Diagnostics). The frequency of MUC1 rs4072037 alleles was significantly different between PAP patients and healthy volunteers (PAP, A/A 46 %, A/G 54 %, G/G 0 %; healthy controls, A/A 30 %, A/G 40 %, G/G 30 %; p = 0.013). Serum KL-6 levels were significantly higher in PAP patients than in controls (p < 0.0001), and significantly higher in PAP patients with A/A genotype than in those with A/G genotype (p = 0.007). Patients with A/A genotype had higher alveolar-arterial oxygen difference (A-aDO2) and lower DLco compared to those with A/G genotype (p = 0.027 and p = 0.012, respectively). Multivariate analysis, Kaplan-Meier analysis and C statistics showed that the rs4072037 A/A genotype was associated with higher rate of disease progression (HR: 5.557, p = 0.014). MUC1 rs4072037 A/A genotype is associated with more severe pulmonary dysfunction and a higher rate of disease progression in PAP patients.