Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Second-generation antipsychotics (SGAs), such as risperidone, clozapine and olanzapine, are the most common drug treatments for schizophrenia. SGAs presented an advantage over first-generation antipsychotics (FGAs), particularly regarding avoidance of extrapyramidal symptoms. However, most SGAs, and to a lesser degree FGAs, are linked to substantial weight gain. This substantial weight gain is a leading factor in patient non-compliance and poses significant risk of diabetes, lipid abnormalities (that is, metabolic syndrome) and cardiovascular events including sudden death. The purpose of this article is to review the advances made in the field of pharmacogenetics of antipsychotic-induced weight gain (AIWG). We included all published association studies in AIWG from December 2006 to date using the Medline and ISI web of knowledge databases. There has been considerable progress reaffirming previous findings and discovery of novel genetic factors. The HTR2C and leptin genes are among the most promising, and new evidence suggests that the DRD2, TNF, SNAP-25 and MC4R genes are also prominent risk factors. Further promising findings have been reported in novel susceptibility genes, such as CNR1, MDR1, ADRA1A and INSIG2. More research is required before genetically informed, personalized medicine can be applied to antipsychotic treatment; nevertheless, inroads have been made towards assessing genetic liability and plausible clinical application.
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PMID:Pharmacogenetics of antipsychotic-induced weight gain: review and clinical implications. 2189 53

Metabolic disturbances are more prevalent in patients with schizophrenia (SCZ) than in the general population. The endocannabinoid system plays an important role in the regulation of dopamine transmission and several metabolic pathways, and the endocannabinoid receptor type 1 gene (CNR1) is considered a candidate gene for both SCZ and metabolic disorders. We examined whether genetic variation in CNR1 was associated with metabolic syndrome (MetS) in a naturalistic cohort of 407 patients with SCZ. The minor alleles of rs6928499, rs1535255, and rs2023239 were nominally associated with a lower risk of MetS [odds ratio (OR), 0.56; 95% confidence interval (CI), 0.37-0.84; P = 0.006; OR, 0.56; 95% CI, 0.37-0.84; P = 0.006; and OR, 0.44; 95% CI, 0.27-0.72; P = 0.001, respectively, adjusted for age, sex, duration of illness, clozapine or olanzapine treatment). These differences were mainly due to differences in high-density lipoprotein cholesterol and fasting glucose but not in body mass index or waist circumference. No significant association of the other polymorphisms (rs806377, rs1049353, rs6454674, and rs806379) with MetS was found. These results provide evidence that the prevalence of MetS is associated with the CNR1 gene in patients with SCZ during long-term treatment with antipsychotic treatment. Further studies are needed to uncover the exact molecular basis for this association, which could provide novel treatment targets for the MetS.
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PMID:CNR1 gene and risk of the metabolic syndrome in patients with schizophrenia. 2342 73

Metabolic side effects such as weight gain and disturbed lipid metabolism are often observed in the treatment of atypical antipsychotic drugs (AAPDs), which contribute to an excessive prevalence of metabolic syndrome among schizophrenic patients. Great individual differences are observed but the underlying mechanisms are still uncertain. Research on pharmacogenomics indicates that gene polymorphisms involved in the pathways controlling food intake and lipid metabolism may play a significant role. In this review, relevant genes (HTR2C, DRD2, LEP, NPY, MC4R, BDNF, MC4R, CNR1, INSIG2, ADRA2A) and genetic polymorphisms related to metabolic side effects of AAPDs especially dyslipidemia were summarized. Apart from clinical studies, in vitro and in vivo evidence is also analyzed to support related theories. The association of central and peripheral mechanisms is emphasized, enabling the possibility of using peripheral gene expression to predict the central status. Novel methodological development of pharmacogenomics is in urgent need, so as to provide references for individualized medication and further to shed some light on the mechanisms underlying AAPD-induced lipid disturbances.
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PMID:Progress in Genetic Polymorphisms Related to Lipid Disturbances Induced by Atypical Antipsychotic Drugs. 3211 76

The purpose of this work was to assess the influence of selected CNR1, MC4R, LEP, FTO and VDR FOKI gene polymorphisms on blood and urine concentration markers of lead, cadmium and arsenic in a population directly exposed to these metals. Eighty-five people exposed to lead, arsenic and cadmium were qualified to take part in the study. Standard urine samples and 25mL of venous blood from each worker were collected to assay basic laboratory and toxicological markers as well as selected single nucleotide polymorphisms (SNPs) within CNR1-cannabinoid receptor 1 gene (rs806368, rs806381, rs1049353, rs12720071), MC4R-melanocortin 4 receptor gene (rs17782313), LEP-leptin promoter gene (rs7799039), FTO-alpha-ketoglutarate-dependent dioxygenase gene (rs9939609) and VDR-vitamin D receptor (rs10735810) genes. It appeared that, except for the MC4R SNP, all the other polymorphisms were found to be associated with various laboratory parameters. Arsenic concentration in urine was associated with all four CNR1 and LEP SNPs, while cadmium concentration in blood was affected by the VDR polymorphism. Moreover, some significant relationships were also observed between CNR1 rs1049353 and FTO rs9939609 gene variants and markers of lead exposure. These results imply SNPs within genes coding for proteins involved in development of metabolic syndrome may be of prognostic value for persons directly exposed to lead, cadmium and arsenic.
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PMID:The Relationship Between Selected CNR1, MC4R, LEP, FTO and VDR Gene Polymorphisms and Several Basic Toxicological Parameters Among Persons Occupationally Exposed to Arsenic, Cadmium and Lead. 3227 84