Clinical characteristics and genetic analysis of a Chinese pedigree of type 2 diabetes complicated with interstitial lung disease
PurposeDiabetes mellitus is a systemic metabolic disorder which may target the lungs and lead to interstitial lung disease. The clinical characteristics and mechanisms of type 2 diabetes mellitus (T2DM) complicated with interstitial lung disease (ILD) have been studied. However, little work has been...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.1050200/full |
| _version_ | 1797951397420859392 |
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| author | Qinghua Zhang Yan Wang Chang Tian Jinyan Yu Yanlei Li Junling Yang |
| author_facet | Qinghua Zhang Yan Wang Chang Tian Jinyan Yu Yanlei Li Junling Yang |
| author_sort | Qinghua Zhang |
| collection | DOAJ |
| description | PurposeDiabetes mellitus is a systemic metabolic disorder which may target the lungs and lead to interstitial lung disease. The clinical characteristics and mechanisms of type 2 diabetes mellitus (T2DM) complicated with interstitial lung disease (ILD) have been studied. However, little work has been done to assess genetic contributions to the development of T2DM complicated with ILD.MethodA pedigree of T2DM complicated with ILD was investigated, and the whole genome re-sequencing was performed to identify the genetic variations in the pedigree. According to the literature, the most valuable genetic contributors to the pathogenesis of T2DM complicated with ILD were screened out, and the related cellular functional experiments were also performed.ResultsA large number of SNPs, InDels, SVs and CNVs were identified in eight subjects including two diabetic patients with ILD, two diabetic patients without ILD, and four healthy subjects from the pedigree. After data analysis according to the literature, MUC5B SNP rs2943512 (A > C) was considered to be an important potentially pathogenic gene mutation associated with the pathogenesis of ILD in T2DM patients. In vitro experiments showed that the expression of MUC5B in BEAS-2B cells was significantly up-regulated by high glucose stimulation, accompanied by the activation of ERK1/2 and the increase of IL-1β and IL-6. When silencing MUC5B by RNA interference, the levels of p-ERK1/2 as well as IL-1β and IL-6 in BEAS-2B cells were all significantly decreased.ConclusionThe identification of these genetic variants in the pedigree enriches our understanding of the potential genetic contributions to T2DM complicated with ILD. MUC5B SNP rs2943512 (A > C) or the up-regulated MUC5B in bronchial epithelial cells may be an important factor in promoting ILD inT2DM patients, laying a foundation for future exploration about the pathogenesis of T2DM complicated with ILD. |
| first_indexed | 2024-04-10T22:29:58Z |
| format | Article |
| id | doaj.art-b17a4908af3d4afba009497219af350c |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T22:29:58Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-b17a4908af3d4afba009497219af350c2023-01-17T06:22:05ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-01-011310.3389/fendo.2022.10502001050200Clinical characteristics and genetic analysis of a Chinese pedigree of type 2 diabetes complicated with interstitial lung diseaseQinghua Zhang0Yan Wang1Chang Tian2Jinyan Yu3Yanlei Li4Junling Yang5Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, ChinaDepartment of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, ChinaDepartment of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, ChinaDepartment of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, ChinaDepartment of Laboratory Medicine, The Second Hospital of Jilin University, Changchun, ChinaDepartment of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, ChinaPurposeDiabetes mellitus is a systemic metabolic disorder which may target the lungs and lead to interstitial lung disease. The clinical characteristics and mechanisms of type 2 diabetes mellitus (T2DM) complicated with interstitial lung disease (ILD) have been studied. However, little work has been done to assess genetic contributions to the development of T2DM complicated with ILD.MethodA pedigree of T2DM complicated with ILD was investigated, and the whole genome re-sequencing was performed to identify the genetic variations in the pedigree. According to the literature, the most valuable genetic contributors to the pathogenesis of T2DM complicated with ILD were screened out, and the related cellular functional experiments were also performed.ResultsA large number of SNPs, InDels, SVs and CNVs were identified in eight subjects including two diabetic patients with ILD, two diabetic patients without ILD, and four healthy subjects from the pedigree. After data analysis according to the literature, MUC5B SNP rs2943512 (A > C) was considered to be an important potentially pathogenic gene mutation associated with the pathogenesis of ILD in T2DM patients. In vitro experiments showed that the expression of MUC5B in BEAS-2B cells was significantly up-regulated by high glucose stimulation, accompanied by the activation of ERK1/2 and the increase of IL-1β and IL-6. When silencing MUC5B by RNA interference, the levels of p-ERK1/2 as well as IL-1β and IL-6 in BEAS-2B cells were all significantly decreased.ConclusionThe identification of these genetic variants in the pedigree enriches our understanding of the potential genetic contributions to T2DM complicated with ILD. MUC5B SNP rs2943512 (A > C) or the up-regulated MUC5B in bronchial epithelial cells may be an important factor in promoting ILD inT2DM patients, laying a foundation for future exploration about the pathogenesis of T2DM complicated with ILD.https://www.frontiersin.org/articles/10.3389/fendo.2022.1050200/fulltype 2 diabetes mellitusinterstitial lung diseaseMUC5Bpedigreewhole genome re-sequencing |
| spellingShingle | Qinghua Zhang Yan Wang Chang Tian Jinyan Yu Yanlei Li Junling Yang Clinical characteristics and genetic analysis of a Chinese pedigree of type 2 diabetes complicated with interstitial lung disease Frontiers in Endocrinology type 2 diabetes mellitus interstitial lung disease MUC5B pedigree whole genome re-sequencing |
| title | Clinical characteristics and genetic analysis of a Chinese pedigree of type 2 diabetes complicated with interstitial lung disease |
| title_full | Clinical characteristics and genetic analysis of a Chinese pedigree of type 2 diabetes complicated with interstitial lung disease |
| title_fullStr | Clinical characteristics and genetic analysis of a Chinese pedigree of type 2 diabetes complicated with interstitial lung disease |
| title_full_unstemmed | Clinical characteristics and genetic analysis of a Chinese pedigree of type 2 diabetes complicated with interstitial lung disease |
| title_short | Clinical characteristics and genetic analysis of a Chinese pedigree of type 2 diabetes complicated with interstitial lung disease |
| title_sort | clinical characteristics and genetic analysis of a chinese pedigree of type 2 diabetes complicated with interstitial lung disease |
| topic | type 2 diabetes mellitus interstitial lung disease MUC5B pedigree whole genome re-sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.1050200/full |
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