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

Fei Chen,1,2,&ast; Jie Zhao,1,&ast; Rubing Mo,1 Xiuxiu Ding,1 Yue Zhang,1 Linhui Huang,1 Tian Xie,1 Yipeng Ding1 1Department 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; 2Department of General Practice, Bai Majing Town Central Health Center, Danzhou City, Hainan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yipeng Ding; Tian Xie, 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, No. 19 Xiuhua Road, Xiuying District, Email [email protected]; [email protected]: 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/m2 (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.Keywords: COPD, ADGRG6, genetic variants, mutant allele