Xu Jingran, Li Li, Ren Jie, Zhong Xuemei, Xie Chengxin, Zheng Aifang, Abudukadier Ayiguzali, Tuerxun Maimaitiaili, Zhang Sujie, Tang Lifeng, Hairoula Dilare, Zou Xiaoguang
Department of Medical College, Shihezi University, Shihezi, China.
Department of Respiratory and Critical Care Medicine, First People's Hospital of Kashi, Kashi, China.
Front Cell Dev Biol. 2022 Feb 7;9:792027. doi: 10.3389/fcell.2021.792027. eCollection 2021.
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 () gene and g.61190482A > G (rs777591A > G, NC_000002.12) in the ubiquitin-specific protease 34 () 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, > .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 in cigarette smoke extract-treated BEAS-2b cells increased significantly compared with those in the control group. Our findings associate the rs777591"AA" genotype as a protector factor in COPD.
遗传因素是慢性阻塞性肺疾病（COPD）发病的重要因素。在中国汉族人群中，已鉴定出大量COPD的风险基因和新的致病基因。相比之下，我们对喀什地区COPD人群（维吾尔族）的遗传学了解甚少。本研究旨在阐明中国喀什地区COPD易感性的遗传图谱。采用全外显子组测序（WES）分析喀什地区三个患有COPD的维吾尔族家庭（8例患者和1例健康对照）。还采用桑格测序法在541例无亲缘关系的维吾尔族COPD患者和534例维吾尔族健康对照中验证WES结果。WES显示72个单核苷酸变异（SNV）、2个缺失和小插入（InDel）、26个拷贝数变异（CNV）和34个结构变异（SV），包括HYDIN轴丝中央对装置蛋白（）基因中的g.71230620T>A（rs12449210T>A，NC_000,016.10）和泛素特异性蛋白酶34（）基因中的g.61190482A>G（rs777591A>G，NC_000002.12）。桑格测序后，我们发现除显性模型外（校正OR = 0.8559，95%CI 0.6568 - 1.115，>0.05），不同遗传模型下的rs777591“AA”可显著降低COPD风险，但rs12449210T>A与COPD无关。在吸烟状况的分层分析中，rs777591“AA”在非吸烟组中显著降低COPD风险。与对照组相比，香烟烟雾提取物处理的BEAS-2b细胞中蛋白和mRNA表达显著增加。我们的研究结果表明rs777591“AA”基因型是COPD的保护因素。
