Weight gain is one of the most serious adverse effects of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight. The objective of our study was to determine whether the LEPR Q223R polymorphism and the LEP promoter 2548G/A polymorphism are associated with obesity in a group of male and female patients using atypical antipsychotic drugs. A cross-sectional study design was used. The study population consisted of 200 patients aged between 18 and 65 years, diagnosed with a psychotic disorder, all of whom had been using an atypical antipsychotic for at least 3 months. The primary outcome measure was the presence of obesity. Determinants were the LEPR Q223R (rs1137101) polymorphism and the LEP promoter 2548G/A single nucleotide polymorphism ([SNP] rs7799039). Of the 200 included patients, 61 (31%) were obese. In females, the LEPR 223QR (adjusted odds ratio, 0.11; 95% confidence interval [CI], 0.02-0.54) and LEPR 223RR (adjusted odds ratio, 0.07; 95% CI, 0.01-0.63) genotypes were associated with a lower risk of obesity. In males, this association was not found. In females, the average body weight was 13.6 kg more (95% CI, 1.11-26.1) in the LEPR 223QQ group compared with the LEPR 223RR group. No significant association was found between the LEP promoter 2548G/A polymorphism and obesity. Taken together, the results of our study show that the LEPR Q223R polymorphism may be associated with obesity in women with a psychotic disorder treated with atypical antipsychotic drugs and stress the importance of stratification for gender when investigating the role of variations of the LEP- and LEPR genes on the metabolic side effects of antipsychotic medications.
The LEPR Q223R polymorphism may be a risk factor for obesity in women with a psychotic disorder treated with atypical antipsychotic drugs. This is in line with earlier findings of our group.
Obesity is one of the most serious common somatic adverse effects of atypical antipsychotic agents. Genetic factors partly determine the individual patients risk of developing obesity during treatment. As weight-regulating mechanisms, such as the leptinergic and serotonergic system, may be interdependent, genetic polymorphisms in these systems also may show interactions. To determine whether combined HTR2CLEP genotype or HTR2C-LEPR genotype are associated with obesity in patients using atypical antipsychotic drugs, a cross-sectional study design was used. The study population included 200 patients aged between 18 and 65 years of age, diagnosed with a psychotic disorder, all of whom had been using an atypical antipsychotic for at least 3 months. Primary outcome measure was presence of obesity (body mass index, >30). Determinants were the combined (HTR2C -759C/T-LEPR Q223R), (HTR2C -759C/T-LEP -2548G/A, (HTR2C rs1414334-LEPR Q223R) and (HTR2C rs1414334-LEP -2548G/A) genotypes. Of the 200 included patients, 61 (31%) were obese. In patients without the HTR2C -759T allele, presence of the LEP -2548G allele was associated with obesity (odds ratio, 2.88; 95% confidence interval, 1.05-7.95). The results of the other analyses showed some nonsignificant trends. The combined (HTR2C -759C/TYLEP -2548G/A) genotype may be a determinant of obesity in patients during treatment with atypical antipsychotic drugs.
In psychiatric practice, pharmacogenetics has the potential to identify patients with an increased risk of unsatisfactory drug responses. Genotype-guided treatment adjustments may increase benefits and reduce harm in these patients; however, pharmacogenetic testing is not (yet) common practice and more pharmacogenetic research in psychiatric patients is warranted. An important precondition for this type of research is the establishment of biobanks. In this paper, we argue that, for the storage of samples in psychiatric biobanks, waiving of consent is not ethically justifiable since the risks cannot be considered minimal and the argument of impracticability does not apply. An opt-out consent procedure is also not justifiable, since it presumes competence while the decisional competence of psychiatric patients needs to be carefully evaluated. We state that an enhanced opt-in consent procedure is ethically necessary, i.e. a procedure that supports the patients' decision-making at the time when the patient is most competent. Nevertheless, such a procedure is not the traditional exhaustive informed consent procedure, since this is not feasible in the case of biobanking.
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