1Am. J. Med. Genet. 2002 Jan 114: 15-23
PMID11840500
TitleMutation analysis of the retinoid X receptor beta, nuclear-related receptor 1, and peroxisome proliferator-activated receptor alpha genes in schizophrenia and alcohol dependence: possible haplotype association of nuclear-related receptor 1 gene to alcohol dependence.
AbstractBecause retinoid cascades are involved in the regulation and development of the central nervous system, including dopaminergic neurons, retinoic acid signaling defects may contribute to schizophrenia and substances dependence. Retinoid X receptors (RXRs) form heterodimer complexes with nuclear-related receptor 1 (NURR1) or with peroxisome proliferator-activated receptors (PPARs). We examined 48 Japanese patients with schizophrenia and 32 patients with alcohol dependence to detect mutations in the retinoid X receptor beta gene (RXRB) on chromosome 6p21.3, the NURR1 gene (NR4A2) on chromosome 2q22-q23, and the PPAR alpha gene (PPARA) on chromosome 22q12.2-13.1. A Val95Ala polymorphism of the RXRB gene, a Val227Ala polymorphism in the PPARA gene, and two synonymous single-nucleotide and CA repeat polymorphisms in the 5' region and 3' untranslated region of the NR4A2 gene were identified. Extended case control samples did not suggest an association between the diseases and the RXRB or PPARA polymorphisms. However, they revealed a significant association between the NR4A2 gene haplotype and alcohol dependence, indicating that 2q22-q23 including the NR4A2 gene locus is a possible genomic region contributing to genetic susceptibility to alcohol dependence.
SCZ Keywordsschizophrenia, schizophrenic
2Eur Neuropsychopharmacol 2013 Jul 23: 749-59
PMID22920733
TitleInvestigation of endocannabinoid system genes suggests association between peroxisome proliferator activator receptor-? gene (PPARA) and schizophrenia.
Abstractschizophrenia (SZ) is a complex psychiatric disorder with a large genetic burden and an estimated hereditability of 80%. A large number of neuroanatomical and psychopharmacological studies suggest a central role of the endocannabinoid (eCB) system in the susceptibility of the disease. To further investigate this hypothesis, we performed an association study with genes codifying for key elements of the eCB system in a sample of 170 schizophrenic patients and 350 healthy controls of Italian ancestry. A total of 57 Tag SNPs (tSNPs) were selected using HapMap CEU population SNP database spanning the following genes: cannabinoid receptor 1 (CNR1), peroxisome proliferator activator receptor-? (PPARA), fatty acid amide hydrolase (FAAH) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). Seven out of the 32 tSNPs within PPARA (rs4253765, rs4263776, rs6007662, rs1800206, rs4253763, rs6008197 and rs4253655) and 3 out of 12 tSNPs within CNR1 (rs1049353, rs7766029 and rs806366) were nominally associated with SZ (uncorrected p<0.05). The same pattern of association was observed in the genotype analysis, with rs4253765 showing the highest level of significance (uncorrected p=210(-3)). None of these associations survived after permutation test. Our findings suggest a potential role for PPARA in the susceptibility to SZ, but further studies on larger independent samples are warranted in order to clarify the involvement of this gene in the pathophysiology of SZ.
SCZ Keywordsschizophrenia, schizophrenic
3Eur Neuropsychopharmacol 2013 Jul 23: 749-59
PMID22920733
TitleInvestigation of endocannabinoid system genes suggests association between peroxisome proliferator activator receptor-? gene (PPARA) and schizophrenia.
Abstractschizophrenia (SZ) is a complex psychiatric disorder with a large genetic burden and an estimated hereditability of 80%. A large number of neuroanatomical and psychopharmacological studies suggest a central role of the endocannabinoid (eCB) system in the susceptibility of the disease. To further investigate this hypothesis, we performed an association study with genes codifying for key elements of the eCB system in a sample of 170 schizophrenic patients and 350 healthy controls of Italian ancestry. A total of 57 Tag SNPs (tSNPs) were selected using HapMap CEU population SNP database spanning the following genes: cannabinoid receptor 1 (CNR1), peroxisome proliferator activator receptor-? (PPARA), fatty acid amide hydrolase (FAAH) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). Seven out of the 32 tSNPs within PPARA (rs4253765, rs4263776, rs6007662, rs1800206, rs4253763, rs6008197 and rs4253655) and 3 out of 12 tSNPs within CNR1 (rs1049353, rs7766029 and rs806366) were nominally associated with SZ (uncorrected p<0.05). The same pattern of association was observed in the genotype analysis, with rs4253765 showing the highest level of significance (uncorrected p=210(-3)). None of these associations survived after permutation test. Our findings suggest a potential role for PPARA in the susceptibility to SZ, but further studies on larger independent samples are warranted in order to clarify the involvement of this gene in the pathophysiology of SZ.
SCZ Keywordsschizophrenia, schizophrenic