{"title":"印度间质性肺疾病（ILD）患者MUC5B （rs35705950）多态性及其与血清Krebs Von Den Lungen-6 （KL-6）和基质金属蛋白酶-7 （MMP7）的关系","authors":"Tanya Athavale, Amita U Athavale, Trisha Samant, Tanaya Tipnis, Namrata Neman, Amrutha Jose, Pooja Jaiswal, Anshu Priya, Manisha Madkaikar, Vandana Pradhan","doi":"10.7759/cureus.93801","DOIUrl":null,"url":null,"abstract":"<p><p>Purpose Krebs von den Lungen-6 (KL-6) and matrix metalloproteinase-7 (MMP7) are established serum biomarkers for interstitial lung disease (ILD). A combination of KL-6 and MMP7 may be a useful screening tool for patients at risk of ILD. However, data on their association with MUC5B promoter polymorphism (rs35705950) in Indian ILD patients are lacking. There is a gap in knowledge of MUC5B genotypes in different subtypes of ILD and the diagnostic cut-offs of serum KL-6 and MMP7 in ILD patients from India. The primary aims of this study were to evaluate the proportion of MUC5B promoter polymorphism in different subtypes of ILD and to establish diagnostic cut-offs for serum KL-6 and MMP7 to distinguish ILD patients from healthy controls. The secondary aim was to investigate whether there was any genotype-phenotype association between the MUC5B genotype and serum biomarker levels. Methods This cross-sectional study was conducted in 200 ILD patients from a tertiary care institute in India. Serum KL-6 and MMP7 levels were measured using ELISA. Genotyping for MUC5B (rs35705950) was performed using DNA extracted from peripheral blood leukocytes. Results Connective tissue disease-associated interstitial lung disease (CTD-ILD) was the most common ILD subtype (45%). KL-6 levels were higher in idiopathic pulmonary fibrosis (IPF) than fibrotic hypersensitivity pneumonitis (fHP) (105.6 ng/mL vs. 65.87 ng/mL; p=0.0409), in patients who died (109.8 ng/mL vs. 68.6 ng/mL; p=0.022), and in the MUC5B (rs35705950) GT/TT genotype (85.07 ng/mL vs. 65.58 ng/mL; p=0.019). MMP7 levels were higher in IPF than CTD-ILD and fHP (14.01 ng/mL vs. 8.690 ng/mL and 7.970 ng/mL; p=0.0175 and p=0.0118, respectively). The minor MUC5B T allele was more frequent in all ILD subtypes. Conclusion This study established an association between MUC5B (rs35705950) promoter polymorphism and higher serum KL-6 levels. The T minor allele had a higher frequency in all ILD subtypes. The study also established cut-offs of serum KL-6 and MMP7 to distinguish between Indian ILD patients and controls.</p>","PeriodicalId":93960,"journal":{"name":"Cureus","volume":"17 10","pages":"e93801"},"PeriodicalIF":1.3000,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495940/pdf/","citationCount":"0","resultStr":"{\"title\":\"MUC5B (rs35705950) Polymorphism and Its Association With Serum Krebs Von Den Lungen-6 (KL-6) and Matrix Metalloproteinase-7 (MMP7) in Patients With Interstitial Lung Disease (ILD) From India.\",\"authors\":\"Tanya Athavale, Amita U Athavale, Trisha Samant, Tanaya Tipnis, Namrata Neman, Amrutha Jose, Pooja Jaiswal, Anshu Priya, Manisha Madkaikar, Vandana Pradhan\",\"doi\":\"10.7759/cureus.93801\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Purpose Krebs von den Lungen-6 (KL-6) and matrix metalloproteinase-7 (MMP7) are established serum biomarkers for interstitial lung disease (ILD). A combination of KL-6 and MMP7 may be a useful screening tool for patients at risk of ILD. However, data on their association with MUC5B promoter polymorphism (rs35705950) in Indian ILD patients are lacking. There is a gap in knowledge of MUC5B genotypes in different subtypes of ILD and the diagnostic cut-offs of serum KL-6 and MMP7 in ILD patients from India. The primary aims of this study were to evaluate the proportion of MUC5B promoter polymorphism in different subtypes of ILD and to establish diagnostic cut-offs for serum KL-6 and MMP7 to distinguish ILD patients from healthy controls. The secondary aim was to investigate whether there was any genotype-phenotype association between the MUC5B genotype and serum biomarker levels. Methods This cross-sectional study was conducted in 200 ILD patients from a tertiary care institute in India. Serum KL-6 and MMP7 levels were measured using ELISA. Genotyping for MUC5B (rs35705950) was performed using DNA extracted from peripheral blood leukocytes. Results Connective tissue disease-associated interstitial lung disease (CTD-ILD) was the most common ILD subtype (45%). KL-6 levels were higher in idiopathic pulmonary fibrosis (IPF) than fibrotic hypersensitivity pneumonitis (fHP) (105.6 ng/mL vs. 65.87 ng/mL; p=0.0409), in patients who died (109.8 ng/mL vs. 68.6 ng/mL; p=0.022), and in the MUC5B (rs35705950) GT/TT genotype (85.07 ng/mL vs. 65.58 ng/mL; p=0.019). MMP7 levels were higher in IPF than CTD-ILD and fHP (14.01 ng/mL vs. 8.690 ng/mL and 7.970 ng/mL; p=0.0175 and p=0.0118, respectively). The minor MUC5B T allele was more frequent in all ILD subtypes. Conclusion This study established an association between MUC5B (rs35705950) promoter polymorphism and higher serum KL-6 levels. The T minor allele had a higher frequency in all ILD subtypes. The study also established cut-offs of serum KL-6 and MMP7 to distinguish between Indian ILD patients and controls.</p>\",\"PeriodicalId\":93960,\"journal\":{\"name\":\"Cureus\",\"volume\":\"17 10\",\"pages\":\"e93801\"},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2025-10-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12495940/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cureus\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.7759/cureus.93801\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/10/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cureus","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.7759/cureus.93801","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/10/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
摘要
Krebs von den Lungen-6 （KL-6）和基质金属蛋白酶-7 （MMP7）是间质性肺疾病（ILD）的血清生物标志物。KL-6和MMP7的组合可能是有ILD风险患者的有用筛查工具。然而，缺乏它们与印度ILD患者MUC5B启动子多态性（rs35705950）相关的数据。在不同ILD亚型的MUC5B基因型和印度ILD患者血清KL-6和MMP7的诊断截止值方面存在知识空白。本研究的主要目的是评估MUC5B启动子多态性在不同ILD亚型中的比例，并建立血清KL-6和MMP7的诊断截止值，以区分ILD患者和健康对照。第二个目的是研究MUC5B基因型与血清生物标志物水平之间是否存在任何基因型-表型关联。方法本横断面研究在印度三级医疗机构的200名ILD患者中进行。ELISA法检测血清KL-6、MMP7水平。采用外周血白细胞提取的DNA进行MUC5B （rs35705950）基因分型。结果结缔组织病相关间质性肺疾病（CTD-ILD）是最常见的ILD亚型（45%）。特发性肺纤维化（IPF）患者的KL-6水平高于纤维化超敏性肺炎（fHP）患者（105.6 ng/mL vs. 65.87 ng/mL, p=0.0409），死亡患者（109.8 ng/mL vs. 68.6 ng/mL, p=0.022）， MUC5B (rs35705950) GT/TT基因型患者（85.07 ng/mL vs. 65.58 ng/mL, p=0.019）。IPF中MMP7水平高于CTD-ILD和fHP （14.01 ng/mL比8.690 ng/mL和7.970 ng/mL, p=0.0175和p=0.0118）。次要的MUC5B T等位基因在所有ILD亚型中更为常见。结论MUC5B （rs35705950）启动子多态性与血清KL-6水平升高存在相关性。T小等位基因在所有ILD亚型中频率较高。该研究还建立了血清KL-6和MMP7的截止值，以区分印度ILD患者和对照组。
MUC5B (rs35705950) Polymorphism and Its Association With Serum Krebs Von Den Lungen-6 (KL-6) and Matrix Metalloproteinase-7 (MMP7) in Patients With Interstitial Lung Disease (ILD) From India.
Purpose Krebs von den Lungen-6 (KL-6) and matrix metalloproteinase-7 (MMP7) are established serum biomarkers for interstitial lung disease (ILD). A combination of KL-6 and MMP7 may be a useful screening tool for patients at risk of ILD. However, data on their association with MUC5B promoter polymorphism (rs35705950) in Indian ILD patients are lacking. There is a gap in knowledge of MUC5B genotypes in different subtypes of ILD and the diagnostic cut-offs of serum KL-6 and MMP7 in ILD patients from India. The primary aims of this study were to evaluate the proportion of MUC5B promoter polymorphism in different subtypes of ILD and to establish diagnostic cut-offs for serum KL-6 and MMP7 to distinguish ILD patients from healthy controls. The secondary aim was to investigate whether there was any genotype-phenotype association between the MUC5B genotype and serum biomarker levels. Methods This cross-sectional study was conducted in 200 ILD patients from a tertiary care institute in India. Serum KL-6 and MMP7 levels were measured using ELISA. Genotyping for MUC5B (rs35705950) was performed using DNA extracted from peripheral blood leukocytes. Results Connective tissue disease-associated interstitial lung disease (CTD-ILD) was the most common ILD subtype (45%). KL-6 levels were higher in idiopathic pulmonary fibrosis (IPF) than fibrotic hypersensitivity pneumonitis (fHP) (105.6 ng/mL vs. 65.87 ng/mL; p=0.0409), in patients who died (109.8 ng/mL vs. 68.6 ng/mL; p=0.022), and in the MUC5B (rs35705950) GT/TT genotype (85.07 ng/mL vs. 65.58 ng/mL; p=0.019). MMP7 levels were higher in IPF than CTD-ILD and fHP (14.01 ng/mL vs. 8.690 ng/mL and 7.970 ng/mL; p=0.0175 and p=0.0118, respectively). The minor MUC5B T allele was more frequent in all ILD subtypes. Conclusion This study established an association between MUC5B (rs35705950) promoter polymorphism and higher serum KL-6 levels. The T minor allele had a higher frequency in all ILD subtypes. The study also established cut-offs of serum KL-6 and MMP7 to distinguish between Indian ILD patients and controls.
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