Association of PCK1 with Body Mass Index and Other Metabolic Features in Patients With Psychotropic Treatments

Abstract

Weight gain is a major health problem among psychiatric populations. It implicates several receptors and hormones involved in energy balance and metabolism. Phosphoenolpyruvate carboxykinase 1 is a rate-controlling enzyme involved in gluconeogenesis, glyceroneogenesis and cataplerosis and has been related to obesity and diabetes phenotypes in animals and humans. The aim of this study was to investigate the association of phosphoenolpyruvate carboxykinase 1 polymorphisms with metabolic traits in psychiatric patients treated with psychotropic drugs inducing weight gain and in general population samples. One polymorphism (rs11552145G > A) significantly associated with body mass index in the psychiatric discovery sample (n = 478) was replicated in 2 other psychiatric samples (n1 = 168, n2 = 188), with AA-genotype carriers having lower body mass index as compared to G-allele carriers. Stronger associations were found among women younger than 45 years carrying AA-genotype as compared to G-allele carriers (-2.25 kg/m, n = 151, P = 0.009) and in the discovery sample (-2.20 kg/m, n = 423, P = 0.0004). In the discovery sample for which metabolic parameters were available, AA-genotype showed lower waist circumference (-6.86 cm, P = 0.008) and triglycerides levels (-5.58 mg/100 mL, P < 0.002) when compared to G-allele carriers. Finally, waist-to-hip ratio was associated with rs6070157 (proxy of rs11552145, r = 0.99) in a population-based sample (N = 123,865, P = 0.022). Our results suggest an association of rs11552145G > A polymorphism with metabolic-related traits, especially in psychiatric populations and in women younger than 45 years.

Personalized prescribing: a new medical model for clinical implementation of psychotropic drugs

“…64 , and for transcriptional coactivators (CREB-regulated transcriptional coactivator 1 [CRTC1]) involved in energy balance, appetite regulation, and glucose homeostasis. [66][67][68][69] There is less information on genes associated with antipsychotic-induced diabetes mellitus and hyperlipidemia. A recent GWAS (N=189) identified no associations with antipsychoticinduced weight gain at the genome-wide threshold, but trends for some variants were observed, variants that should be investigated further.…”

Association of variants in SH2B1 and RABEP1 with worsening of low-density lipoprotein and glucose parameters in patients treated with psychotropic drugs

“…In addition, numerous single nucleotide polymorphisms (SNPs) within genes involved in other pathways of metabolism regulation (e.g. enzymes, receptors or transcriptional coactivators involved in leptin-melanocortin pathways, genes involved in cholesterol and/or in glucose homeostasis) were also associated with weight gain in psychiatric patients taking psychotropic drugs (18)(19)(20)(21)(22).…”

“…A growing body of evidence suggests that obesity and psychiatric diseases share common etiological pathways, which may be illustrated by the observed synergistic influence of genes associated with obesity and with psychiatric illness on cardiometabolic parameters (23). In addition, recent pharmacogenetic studies have shown stronger influence on obesity phenotypes of some BMI-associated genes in the psychiatric population treated with weight gain inducing psychotropic drugs compared to the general population (19)(20)(21). Unfortunately, it is unknown to which extent the 97 variants associated with BMI in the general population are associated with other cardiometabolic phenotypes in the psychiatric population, despite that such populations are at very high risk for cardiometabolic disorders.…”