Gene–gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics

Abstract

The use of atypical antipsychotics (AAPs) is associated with increasing the risk of the metabolic syndrome (MetS), which is an important risk factor for cardiovascular disease and diabetes. Two insulin-induced gene (INSIG) isoforms, designated INSIG-1 and INSIG-2 encode two proteins that mediate feedback control of lipid metabolism. In this genetic case-control study, we investigated whether the common variants in INSIG1 and INSIG2 genes were associated with MetS in schizophrenic patients treated with atypical antipsychctics. The study included 456 schizophrenia patients treated with clozapine (n ¼ 171), olanzapine (n ¼ 91) and risperidone (n ¼ 194), for an average of 45.5±27.6 months. The prevalence of MetS among all subjects was 22.8% (104/456). Two single-nucleotide polymorphisms (SNPs) of the INSIG1 gene and seven SNPs of the INSIG2 gene were chosen as haplotypetagging SNPs. In single-marker-based analysis, the INSIG2 rs11123469-C homozygous genotype was found to be more frequent in the patients with MetS than those without MetS (P ¼ 0.001). In addition, haplotype analysis showed that the C-C-C haplotype of rs11123469-rs10185316-rs1559509 of the INSIG2 gene significantly increased the risk of MetS (P ¼ 0.0023). No significant associations were found between polymorphisms of INSIG1 gene and MetS, however, INSIG1 and INSIG2 interactions were found in the significant 3-locus and 4-locus gene-gene interaction models (P ¼ 0.003 and 0.012, respectively). The results suggest that the INSIG2 gene may be associated with MetS in patients treated with AAPs independently or in an interactive manner with INSIG1.

Association between SREBF2 gene polymorphisms and metabolic syndrome in clozapine-treated patients with schizophrenia

“…In this study, the overall prevalence of MetS in the 621 patients with clozapine treatment was 41.8% (260/621), which is higher than that (22%) reported by another study in a Han Chinese sample (Liou et al, 2012). The possible reasons for this could be due to longer duration of drug usage, and the clozapine received in our study, which induces high potency for MetS.…”

The rs1277306 Variant of the <b><i>REST</i></b> Gene Confers Susceptibility to Cognitive Aging in an Elderly Taiwanese Population

“…The quality of the isolated genomic DNA was evaluated using agarose gel electrophoresis, and the quantity was determined by spectrophotometry [16,17]. SNP genotyping was carried out using the custom Taiwan BioBank chips and run on the Axiom Genome-Wide Array Plate System (Affymetrix, Santa Clara, CA, USA).…”

The ENPP1 K121Q polymorphism is associated with type 2 diabetes and related metabolic phenotypes in a Taiwanese population

“…The main weakness of this study is an insufficient sample size of obese cases in the context of polygenic studies (Li and Meyre, 2013;Lin et al, 2009;Liou et al, 2012;Lane et al, 2012). In future work, prospective clinical trials with very large sample sizes are necessary to facilitate a thorough evaluation of the association of this SNP with T2D, obesity, and T2D/obesity-related metabolic traits Liou et al, 2012;Lane et al, 2012).…”