Association of GLP1R variants rs2268641 and rs6923761 with obesity and other metabolic parameters in a Polish cohort

Abstract

IntroductionObesity is a complex disease associated with excessive fat accumulation and numerous metabolic complications. So far, many factors leading to the development of this disorder have been identified, including genetic susceptibility. Various studies linked GLP1R variants with anthropometric and metabolic parameters, suggesting the role of the variation in this gene in metabolic health.ObjectiveThe aim of this study is to investigate the association of two single nucleotide variants of GLP1R gene, rs2268641 and rs6923761, with excessive weight, metabolic syndrome, anthropometric measurements and selected metabolic parameters.MethodsNormal-weight subjects (n= 340, control group) and subjects with excessive body mass (n = 600, study group) participated in this study. For all participants, anthropometric measurements and metabolic parameters were collected, and genotyping of the two single nucleotide variants of GLP1R gene, rs2268641 and rs6923761, was performed using the high-resolution melting curve analysis.ResultsSignificant differences in the genotype distribution of rs2268641 were found, where homozygous TT genotype was significantly less frequent in the study group with excessive body mass (OR=0.66; p=0.0298). For rs6923761, A allele and homozygous AA genotype were significantly more frequent in the study group with excessive weight than in the control group (OR=1.27; p=0.0239 and OR=1.69; p=0.0205, respectively). The association of studied variants with metabolic parameters was found for rs6923761. For this variant, AA carriers had higher body mass in comparison to GG carriers (p=0.0246), and AA carriers had higher glucose concentration in comparison to AG carriers (p=0.0498). We did not find an association of rs2268641 and rs6923761 with metabolic syndrome.ConclusionIn our study, AA carriers of rs6923761 had higher risk of excessive body mass, whereas TT carriers of rs2268641 had lower risk of being overweight. Moreover, homozygous carriers of the minor allele of rs6923761 had higher glucose concentration in comparison to heterozygous subjects. None of the studied variants were associated with metabolic syndrome in the studied population.

Functionally Significant Variants in Genes Associated with Abdominal Obesity: A Review

“…Variants rs2268641 and rs6923761 in this gene correlate with a high BMI [ 102 , 103 ]. Carriers of the AA genotype of rs6923761 have a higher risk of obesity and higher glucose levels [ 104 ]. Variant rs10305492 in a European population [ 105 ] and rs3765467 and rs10305492 in a Chinese population [ 106 ] have been implicated in metabolic syndrome and a higher risk of T2DM.…”

Adipose gene expression profiles and their associations with adaptations in Northern Finncattle, Mirandesa cattle, Yakutian cattle and Holstein cattle

“…In tailhead adipose tissue, GLP1R was upregulated in females. In addition to being associated with feed e ciency, this gene is also associated with obesity in humans [78], and GLP-1 analogues such as semaglutide are used for the treatment of obesity and diabetes [79]. These cattle do not eat industrially produced food.…”

Genetic variants of the glucagon-like receptor-1 in obesity

“…At the same time, Michałowska et al revealed a tendency to hyperglycemia in carriers of the AA rs6923761 genotype, compared with carriers of the AG rs6923761 genotype, but found no association with the metabolic syndrome, which also coincided with the results of our studies. 48 Sathananthan et al 49 , also Daniel Antonio de Luis et al demonstrated that GLP-1R in heterozygotes for SNV rs6923761 of the GLP1R gene (GA genotype) has a low receptor affinity for GLP-1, which leads to relatively reduced insulin secretion in response to GLP-1 infusion and, as a result, promotes the development of hyperglycemia. Individuals with the A allele of SNV rs6923761 of the GLP1R gene and morbid obesity have higher levels of triglycerides, insulin, and insulin resistance.…”