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Whole-Exome Sequencing Implicates the USP34 rs777591A > G Intron Variant in Chronic Obstructive Pulmonary Disease in a Kashi Cohort
Genetic factors are important factors in chronic obstructive pulmonary disease (COPD) onset. Plenty of risk and new causative genes for COPD have been identified in patients of the Chinese Han population. In contrast, we know considerably little concerning the genetics in the Kashi COPD population (...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8859106/ https://www.ncbi.nlm.nih.gov/pubmed/35198563 http://dx.doi.org/10.3389/fcell.2021.792027 |
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author | Xu, Jingran Li, Li Ren, Jie Zhong, Xuemei Xie, Chengxin Zheng, Aifang Abudukadier, Ayiguzali Tuerxun, Maimaitiaili Zhang, Sujie Tang, Lifeng Hairoula, Dilare Zou, Xiaoguang |
author_facet | Xu, Jingran Li, Li Ren, Jie Zhong, Xuemei Xie, Chengxin Zheng, Aifang Abudukadier, Ayiguzali Tuerxun, Maimaitiaili Zhang, Sujie Tang, Lifeng Hairoula, Dilare Zou, Xiaoguang |
author_sort | Xu, Jingran |
collection | PubMed |
description | Genetic factors are important factors in chronic obstructive pulmonary disease (COPD) onset. Plenty of risk and new causative genes for COPD have been identified in patients of the Chinese Han population. In contrast, we know considerably little concerning the genetics in the Kashi COPD population (Uyghur). This study aims at clarifying the genetic maps regarding COPD susceptibility in Kashi (China). Whole-exome sequencing (WES) was used to analyze three Uyghur families with COPD in Kashi (eight patients and one healthy control). Sanger sequencing was also used to verify the WES results in 541 unrelated Uyghur COPD patients and 534 Uyghur healthy controls. WES showed 72 single nucleotide variants (SNVs), two deletions, and small insertions (InDels), 26 copy number variants (CNVs), and 34 structural variants (SVs), including g.71230620T > A (rs12449210T > A, NC_000,016.10) in the HYDIN axonemal central pair apparatus protein (HYDIN) gene and g.61190482A > G (rs777591A > G, NC_000002.12) in the ubiquitin-specific protease 34 (USP34) gene. After Sanger sequencing, we found that rs777591“AA” under different genetic models except for the dominant model (adjusted OR = 0.8559, 95%CI 0.6568–1.115, p > .05), could significantly reduce COPD risk, but rs12449210T > A was not related to COPD. In stratified analysis of smoking status, rs777591“AA” reduced COPD risk significantly among the nonsmoker group. Protein and mRNA expression of USP34 in cigarette smoke extract-treated BEAS-2b cells increased significantly compared with those in the control group. Our findings associate the USP34 rs777591“AA” genotype as a protector factor in COPD. |
format | Online Article Text |
id | pubmed-8859106 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88591062022-02-22 Whole-Exome Sequencing Implicates the USP34 rs777591A > G Intron Variant in Chronic Obstructive Pulmonary Disease in a Kashi Cohort Xu, Jingran Li, Li Ren, Jie Zhong, Xuemei Xie, Chengxin Zheng, Aifang Abudukadier, Ayiguzali Tuerxun, Maimaitiaili Zhang, Sujie Tang, Lifeng Hairoula, Dilare Zou, Xiaoguang Front Cell Dev Biol Cell and Developmental Biology Genetic factors are important factors in chronic obstructive pulmonary disease (COPD) onset. Plenty of risk and new causative genes for COPD have been identified in patients of the Chinese Han population. In contrast, we know considerably little concerning the genetics in the Kashi COPD population (Uyghur). This study aims at clarifying the genetic maps regarding COPD susceptibility in Kashi (China). Whole-exome sequencing (WES) was used to analyze three Uyghur families with COPD in Kashi (eight patients and one healthy control). Sanger sequencing was also used to verify the WES results in 541 unrelated Uyghur COPD patients and 534 Uyghur healthy controls. WES showed 72 single nucleotide variants (SNVs), two deletions, and small insertions (InDels), 26 copy number variants (CNVs), and 34 structural variants (SVs), including g.71230620T > A (rs12449210T > A, NC_000,016.10) in the HYDIN axonemal central pair apparatus protein (HYDIN) gene and g.61190482A > G (rs777591A > G, NC_000002.12) in the ubiquitin-specific protease 34 (USP34) gene. After Sanger sequencing, we found that rs777591“AA” under different genetic models except for the dominant model (adjusted OR = 0.8559, 95%CI 0.6568–1.115, p > .05), could significantly reduce COPD risk, but rs12449210T > A was not related to COPD. In stratified analysis of smoking status, rs777591“AA” reduced COPD risk significantly among the nonsmoker group. Protein and mRNA expression of USP34 in cigarette smoke extract-treated BEAS-2b cells increased significantly compared with those in the control group. Our findings associate the USP34 rs777591“AA” genotype as a protector factor in COPD. Frontiers Media S.A. 2022-02-07 /pmc/articles/PMC8859106/ /pubmed/35198563 http://dx.doi.org/10.3389/fcell.2021.792027 Text en Copyright © 2022 Xu, Li, Ren, Zhong, Xie, Zheng, Abudukadier, Tuerxun, Zhang, Tang, Hairoula and Zou. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Xu, Jingran Li, Li Ren, Jie Zhong, Xuemei Xie, Chengxin Zheng, Aifang Abudukadier, Ayiguzali Tuerxun, Maimaitiaili Zhang, Sujie Tang, Lifeng Hairoula, Dilare Zou, Xiaoguang Whole-Exome Sequencing Implicates the USP34 rs777591A > G Intron Variant in Chronic Obstructive Pulmonary Disease in a Kashi Cohort |
title | Whole-Exome Sequencing Implicates the USP34 rs777591A > G Intron Variant in Chronic Obstructive Pulmonary Disease in a Kashi Cohort |
title_full | Whole-Exome Sequencing Implicates the USP34 rs777591A > G Intron Variant in Chronic Obstructive Pulmonary Disease in a Kashi Cohort |
title_fullStr | Whole-Exome Sequencing Implicates the USP34 rs777591A > G Intron Variant in Chronic Obstructive Pulmonary Disease in a Kashi Cohort |
title_full_unstemmed | Whole-Exome Sequencing Implicates the USP34 rs777591A > G Intron Variant in Chronic Obstructive Pulmonary Disease in a Kashi Cohort |
title_short | Whole-Exome Sequencing Implicates the USP34 rs777591A > G Intron Variant in Chronic Obstructive Pulmonary Disease in a Kashi Cohort |
title_sort | whole-exome sequencing implicates the usp34 rs777591a > g intron variant in chronic obstructive pulmonary disease in a kashi cohort |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8859106/ https://www.ncbi.nlm.nih.gov/pubmed/35198563 http://dx.doi.org/10.3389/fcell.2021.792027 |
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