CASyM winter school of Systems Medicine took place between March 29th and April 1st 2017 in Ljubljana, Slovenia and is entitled »The 3rd SysBioMed hands-on tutorial: Systems Medicine Approaches in Personalized Medicine«
1Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia,2Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Objective: The weight lowering potential of glucagon-like peptide 1 (GLP1) receptor agonists (RAs) is inter-individually different and clinically unpredictable. The potential role of genetic variability of GLP1 receptor (GLP1R) on body weight response to GLP1 RA has not yet been evaluated. The aim of the study was to assess the effect of common non-synonymous GLP1R single nucleotide polymorphisms (SNPs) rs6923761 and rs10305420 on weight loss in response to long acting GLP1 RA liraglutide in obese women with PCOS. The GLP1R SNP rs6923761 was previously associated with pathogenesis of obesity, whereas rs10305420 has not yet been investigated as a contributing factor in weight reduction. Methods: 57 obese women with PCOS (aged 30.7 ± 7.0, BMI 38.6 ± 5.3 kg/m2) were assigned to liraglutide 1.2 mg QD sc. for 12 weeks. They were genotyped for GLP1R rs6923761 and rs10305420. Changes of body mass, BMI, waist circumference and visceral adipose tissue (VAT) area were measured before and at the end of the study. Results: After treatment intervention women lost on average 3.96 ± 3.24 kg (P<0.001), BMI was reduced for 1.44 ± 1.22 kg/m2 (P<0.001), waist circumference for 3.31 ± 4.13 cm (P<0.001) and VAT area for 7.10 ± 18.76 cm2 (P=0.002). Twenty (35.1%) out of 57 subjects were good responders and lost 5 % or more of their initial body weight. Carriers of at least one polymorphic rs10305420 allele had worse treatment response compared to carriers of two wild type alleles (OR=0.27, 95% CI=0.09-0.85, P=0.025). Carriers of at least one polymorphic rs6923761 allele tended to have better treatment response compared to carriers of two wild type alleles, but the difference was not statistically significant (OR=3.06, 95% CI=0.96-9.74, P=0.058). Conclusion: GLP1R rs10305420 polymorphism accounts for inter-individual differences in response to liraglutide regarding weight loss in obese women with PCOS. Knowledge of the patients’ specific polymorphic genotype of GLP1R could be one of the contributing factors in the development of an efficient treatment algorithm tailored to intra-individually specific responding potential of obese individuals. Future studies will determine whether such genetic variation may be clinically useful in prediction of the weight lowering potential of GLP1 RAs in obese individuals.
2006 - University of Ljubljana, Faculty of Medicine, Center for Functional Genomics and Bio-chips.