Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atypical antipsychotics are nowadays the most widely used drugs to treat schizophrenia and other psychosis. Unfortunately, some of them can cause major metabolic adverse effects, such as weight gain, dyslipidemia and type 2 diabetes. The underlying lipogenic mechanisms of the antipsychotic drugs are not known, but several studies have focused on a central effect in the hypothalamic control of appetite regulation and energy expenditure. In a functional convergent genomic approach we recently used a cellular model and demonstrated that orexigenic antipsychotics that induce weight gain activate the expression of lipid biosynthesis genes controlled by the sterol regulatory element-binding protein (SREBP) transcription factors. We therefore hypothesized that the major genes involved in the SREBP activation of fatty acids and cholesterol production (SREBF1, SREBF2, SCAP, INSIG1 and INSIG2) would be strong candidate genes for interindividual variation in drug-induced weight gain. We genotyped a total of 44 HapMap-selected tagging single nucleotide polymorphisms in a sample of 160 German patients with schizophrenia that had been monitored with respect to changes in body mass index during antipsychotic drug treatment. We found a strong association (P=0.0003-0.00007) between three markers localized within or near the INSIG2 gene (rs17587100, rs10490624 and rs17047764) and antipsychotic-related weight gain. Our finding is supported by the recent involvement of the INSIG2 gene in obesity in the general population and implicates SREBP-controlled lipogenesis in drug-induced metabolic adverse effects.
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PMID:Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects? 1819 16

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