Effect of GLP-1R rs2254336 and rs3765467 polymorphisms on gastrointestinal adverse reactions in type 2 diabetes patients treated with liraglutide

• Published in: European journal of clinical pharmacology Vol. 78; no. 4; pp. 589 - 596
• Main Authors: Long, Jiangchuan, Liu, Yongjian, Duan, Yaqian, Li, Yang, Yang, Gangyi, Ren, Ziyu, Tao, Wei, Liu, Dongfang
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2022; Springer Nature B.V
• Subjects: Alleles; Antidiabetics; Biomedical and Life Sciences; Biomedicine; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; Female; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide-1 Receptor - genetics; Humans; Hypoglycemic Agents - adverse effects; Liraglutide - adverse effects; Male; Nausea; Pharmacogenetics; Pharmacology/Toxicology; Polymorphism, Single Nucleotide; Side effects; Single-nucleotide polymorphism; Single-nucleotide polymorphism; Gastrointestinal adverse reaction; Type 2 diabetes mellitus; Liraglutide; Glucagon-like peptide-1 receptor
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-021-03225-7

Purpose Gastrointestinal adverse reactions (GIARs) to liraglutide exhibit significant individual differences in type 2 diabetes. This study investigated the association between glucagon-like peptide-1 receptor ( GLP-1R ) single-nucleotide polymorphisms (SNPs) and GIARs. Methods Adverse events of liraglutide were observed in 376 T2DM patients. Seven tag SNPs at GLP-1R were sequenced in 152 participants. The influencing factors of GIARs and the genetic model of tag SNPs were examined by logistic regression analysis. The relationship between the tag SNPs and GIARs was determined by the chi-square test and cochran-armitage trend test. Multifactor dimensionality reduction (MDR) analysis was used to explore interactive analysis in GIARs risk. Results Twenty-nine percent of subjects had side effects, mainly GIARs. Nausea was the most common GIARs. Compared with males, females were more likely to develop GIARs ( P  = 0.043, OR = 1.895, 95% CI: 1.021–3.517). The T allele at GLP-1R rs2254336 ( P  = 0.028) and the A allele at GLP-1R rs3765467 ( P  = 0.007) were associated with GIARs of liraglutide. As the number of rs2254336 T alleles ( P  = 0.014) or rs3765467 A alleles ( P  = 0.008) increased, the subjects tended to develop GIARs. MDR analysis identified that there were no significant interactions among rs2254336, rs3765467 and sex. Conclusion Our results suggest that female sex, the T allele at GLP-1R rs2254336 and the A allele at GLP-1R rs3765467 could be predictors of GIARs with liraglutide in T2DM patients.