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黏附性G蛋白偶联受体ADGRG6中的基因变异与中国南方汉族老年人群慢性阻塞性肺疾病易感性增加有关。

Genetic Variants in the Adhesive G Protein-Coupled Receptor ADGRG6 are Associated with Increased Susceptibility to COPD in the Elderly Han Chinese Population of Southern China.

作者信息

Chen Fei, Zhao Jie, Mo Rubing, Ding Xiuxiu, Zhang Yue, Huang Linhui, Xie Tian, Ding Yipeng

机构信息

Department of Respiratory and Critical Care Medicine, Hainan Affiliated Hospital of Hainan Medical University, Hainan General Hospital, Haikou City, Hainan Province, People's Republic of China.

Department of General Practice, Bai Majing Town Central Health Center, Danzhou City, Hainan Province, People's Republic of China.

出版信息

Int J Chron Obstruct Pulmon Dis. 2024 Dec 3;19:2599-2610. doi: 10.2147/COPD.S478095. eCollection 2024.

Abstract

BACKGROUND

Mutations in ADGRG6 are associated with a variety of cancers and multiple types of diseases. However, the impact of genetic variations in ADGRG6 on chronic obstructive pulmonary disease (COPD) susceptibility has not yet been evaluated.

METHODS

Considering the high prevalence of COPD among the elderly population in China, this study specifically targets the elderly Han population in Southern China as the study subject. Following the acquisition of participants' whole-genome DNA, genotyping was conducted using the Agena MassARRAY platform. The online tool 'SNPStats', which utilizes logistic regression, was employed to analyze and assess the correlation. Multi-factor dimensionality reduction was utilized to clarify the impact of "SNP-SNP" interactions on COPD risk. The False-Positive Report Probability (FPRP) was applied to determine whether significant results are noteworthy findings.

RESULTS

The mutant allele "C" of rs11155242 was a protective genetic factor against COPD susceptibility (OR = 0.57, 95% CI = 0.36 to 0.91, p = 0.017). The heterozygous mutant genotype "CA" of rs11155242 was found to be significantly associated with reduced COPD risk (CA Vs AA: OR = 0.53, 95% CI = 0.32 to 0.90, p = 0.018). ADGRG6-rs11155242 was found to be strongly associated with a reduced risk of COPD in males, non-smokers, and subjects with a BMI below 24 kg/m (OR < 1, p < 0.05). The FPRP analysis indicated that the positive results identified in this study are noteworthy new findings.

CONCLUSION

The mutant allele "C" and mutant genotype "CA" of rs11155242 act as protective genetic factors against COPD susceptibility. This study will provide a new research direction for the personalized prevention and treatment of COPD in the elderly Han population in southern China, and lay a potential scientific basis.

摘要

背景

ADGRG6基因的突变与多种癌症和多种类型的疾病相关。然而,ADGRG6基因变异对慢性阻塞性肺疾病(COPD)易感性的影响尚未得到评估。

方法

考虑到COPD在中国老年人群中的高患病率,本研究专门以中国南方的老年汉族人群为研究对象。在获取参与者的全基因组DNA后,使用Agena MassARRAY平台进行基因分型。利用采用逻辑回归的在线工具“SNPStats”来分析和评估相关性。采用多因素降维法来阐明“SNP-SNP”相互作用对COPD风险的影响。应用假阳性报告概率(FPRP)来确定显著结果是否为值得关注的发现。

结果

rs11155242的突变等位基因“C”是抵抗COPD易感性的保护性遗传因素(比值比=0.57,95%置信区间=0.36至0.91,p=0.017)。发现rs11155242的杂合突变基因型“CA”与降低的COPD风险显著相关(CA与AA相比:比值比=0.53,95%置信区间=0.32至0.90,p=0.018)。发现ADGRG6-rs11155242与男性、非吸烟者以及体重指数低于24kg/m²的受试者中降低的COPD风险密切相关(比值比<1,p<0.05)。FPRP分析表明,本研究中确定的阳性结果是值得关注的新发现。

结论

rs11155242的突变等位基因“C”和突变基因型“CA”是抵抗COPD易感性的保护性遗传因素。本研究将为中国南方老年汉族人群COPD的个性化防治提供新的研究方向,并奠定潜在的科学基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29d1/11624663/0213c383ea95/COPD-19-2599-g0001.jpg

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