Clinical characteristics and genetic analysis of a Chinese pedigree of type 2 diabetes complicated with interstitial lung disease

Qinghua Zhang; Yan Wang; Chang Tian; Jinyan Yu; Yanlei Li; Junling Yang

doi:10.3389/fendo.2022.1050200

Clinical characteristics and genetic analysis of a Chinese pedigree of type 2 diabetes complicated with interstitial lung disease

Front Endocrinol (Lausanne). 2023 Jan 17:13:1050200. doi: 10.3389/fendo.2022.1050200. eCollection 2022.

Authors

Qinghua Zhang¹, Yan Wang¹, Chang Tian¹, Jinyan Yu¹, Yanlei Li², Junling Yang¹

Affiliations

¹ Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, China.
² Department of Laboratory Medicine, The Second Hospital of Jilin University, Changchun, China.

Abstract

Purpose: Diabetes 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.

Method: A 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.

Results: A 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.

Conclusion: The 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.

Keywords: MUC5B; interstitial lung disease; pedigree; type 2 diabetes mellitus; whole genome re-sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / genetics
East Asian People
Humans
Interleukin-6
Lung Diseases, Interstitial* / complications
Lung Diseases, Interstitial* / genetics
Pedigree

Substances

Interleukin-6

Grants and funding

This study was supported by grants from the Science and Technology Department of Jilin Province (20190201279JC), and the Finance Department of Jilin Province (20106145).