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Case Reports 2013; 34(3): 173-176 PubMed PMID: 23685414 Citation  Keywords:  Amino Acid Substitution:genetics, Chromosomes, Human, X, Female, Humans, Insulin Receptor Substrate Proteins:genetics, Middle Aged, Schizophrenia, Paranoid:genetics, Signal Transduction:genetics,.   

: This report deals with a female patient with schizophrenia who was found to have a mutation in the insulin receptor substrate-4 gene that is located on chromosome Xq22.3. Since this mutation is expected to change amino acid coding from histidine to tyrosine and cause an altered insulin receptor substrate-4 protein, and the insulin receptor substrate-4 protein may be involved in neuronal growth and function in the brain, it is possible that it is this insulin receptor substrate-4 gene mutation that underlies this patient's schizophrenia development....

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Journal Article 2012; 33(3): 321-330 PubMed PMID: 22635093 Citation  Keywords:  Adult, Case-Control Studies, Databases, Genetic, Female, Genetic Predisposition to Disease:genetics, Genotype, Humans, Insulin Receptor Substrate Proteins:genetics, Male, Middle Aged, Polymorphism, Single Nucleotide:genetics, Schizophrenia:genetics,.   

OBJECTIVES: Since there are clear indications that schizophrenia is a systemic disorder, we sought for a common molecular basis for schizophrenia abnormalities in brain and body. Our hypothesis was that an impaired insulin and insulin-like growth factor signalling in cells might underlie changes in both brain and body in schizophrenia. In this regard, the insulin receptor substrates 1-4, linking both the insulin and insulin-like growth factor-1 receptors with intracellular pathways, might be of interest to study genetically. In the present study, we chose to study the insulin receptor substrate-3 (IRS-3) gene as a candidate gene in schizophrenia.

METHODS: The IRS-3 gene of 93 patients with the diagnosis of schizophrenia according to DSM-IV criteria and 57 healthy control subjects was screened for DNA sequence variations, followed by case-control analyses of total 10 detected polymorphisms.

RESULTS: The A/G genotype of the single nucleotide polymorphism (SNP) rs117078492 in the IRS-3 gene occurred in 5.3% of the control subjects compared with in 0% of the patients (p=0.05). Similarly, the haplotypes 5 and 3X, constructed from polymorphisms in the IRS-3 gene and including the A allele of this A/G SNP, occurred only in the control subjects and not in the patients (5.3% vs 0%, p=0.05).

CONCLUSION: Our findings suggest that individuals carrying the A allele of this A/G SNP in the IRS-3 gene as well as the estimated haplotypes 5 or 3X including this A allele, have a protection against schizophrenia development....

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Journal Article 2011; 32(5): 634-640 PubMed PMID: 22167131 Citation  Keywords:  Adult, Body Mass Index, Female, Genetic Predisposition to Disease:epidemiology, Genetic Variation:genetics, Genotype, Humans, Insulin Receptor Substrate Proteins:genetics, Male, Middle Aged, Obesity:epidemiology, Polymorphism, Single Nucleotide, Schizophr.   

OBJECTIVES: The insulin receptor substrate-4 (IRS-4) protein is highly expressed in the hypothalamus that plays a main role in the regulation of body weight. Therefore, as overweight and obesity are more frequent in patients with schizophrenia compared to the general population, this study was undertaken to investigate potential associations between body mass index (BMI) or height and polymorphisms in the IRS-4 gene in schizophrenia patients and healthy controls.

METHODS: The IRS-4 gene of 93 patients and 59 controls was screened for DNA sequence variations, and then 10 detected single nucleotide polymorphisms (SNPs) were investigated in relation to BMI and height of patients and controls.

RESULTS: Mean BMI was higher in patients than in controls, whereas there was no difference regarding height. Significant associations were found between patients' BMI and genotypes of six SNPs (rs1801164, rs80131334, rs41307415, rs73253702, rs1801162, rs2073114) or a haplotype including these six SNPs. In contrast, no associations were found between BMI or height of controls, or height of patients, and the genotypes or haplotypes.

CONCLUSION: This study clearly demonstrates associations between BMI and IRS-4 variants in schizophrenia patients, but not in healthy controls, pointing to a possible involvement of IRS-4 in the control of body weight in schizophrenia....

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Journal Article 2011; 32(1): 52-58 PubMed PMID: 21407155 Citation  Keywords:  Adult, Case-Control Studies, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Insulin Receptor Substrate Proteins:genetics, Male, Middle Aged, Point Mutation, Polymorphism, Single Nucleotide, Schizophrenia:genetics,.   

OBJECTIVES: Since there are clear indications that schizophrenia is a systemic disorder, we sought for a common molecular basis for schizophrenia abnormalities in brain and body. Our hypothesis was that an impaired insulin/ insulin-like growth factor signalling in cells might underlie both structural and functional brain changes and peripheral abnormalities in schizophrenia. No associations between polymorphisms in the genes for insulin-like growth factor 1 or its receptor and schizophrenia have been reported. However, the insulin receptor substrates 1-4 linking both the insulin and insulin-like growth factor 1 receptors with intracellular pathways have not been extensively studied in schizophrenia. In this study, we therefore chose to study the insulin receptor substrate-4 (IRS-4) gene as a candidate gene in schizophrenia.

METHODS: The IRS-4 gene of 93 patients and 59 control subjects was screened for DNA sequence variations, followed by case-control analyses of 10 detected single nucleotide polymorphisms.

RESULTS: No significant genotype, allele or haplotype associations were found with the schizophrenia illness. However, one female patient with paranoid schizophrenia had an IRS-4 gene mutation at position 107863596, resulting in a change in amino acid coding from histidine to tyrosine at position 879.

CONCLUSIONS: Although this study supports the view that the IRS-4 gene is not of major importance for the aetiology of the vast majority of schizophrenia cases, our finding of this single patient with schizophrenia and a mutation in the IRS-4 gene may point to that the insulin/ insulin-like growth factor signalling system in cells is still of interest in the future search for schizophrenia genes....

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Journal Article 2006; 27(1-2): 219-224 PubMed PMID: 16648810 Citation  Keywords:  3-Hydroxysteroid Dehydrogenases:genetics, Adrenal Cortex Hormones:metabolism, Alleles, Child, China:epidemiology, Female, Gene Frequency, Genotype, Gonadal Steroid Hormones:blood, Humans, Insulin Receptor Substrate Proteins, Molecular Sequence Data, Phosp.   

OBJECTIVES: In order to investigate whether the variances in the candidate genes (Insulin receptor substrate IRS-1, beta3-adrenergic receptor ADRB3, 3 beta-hydro-xysteroid dehydrogenase HSD3B2, glucocorticoid receptor GRL and 21-hydroxylase CYP21) which affect the metabolism of adrenal steroids hormone and body composition, are associated with precocious puberty in Chinese girls.

METHODS: PCR-RFLP analysis method was applied in the typing of six activity SNPs in five genes in two groups: 176 precocious puberty girls as case and 192 healthy girls as control.

RESULTS: The typing results showed that the frequencies of the allele CYP21 L282 polymorphism were 32.7% and 32.6% in case and control groups (P=0.518), respectively. For IRS-1 R972, they were 0.6% in cases and 2.3% in controls (P=0.043), for ADRB3 R64, 13.6% in cases and 12% in controls (P=0. 378), and for GRL S363, 7.4% in cases and 5.73% in controls (P=0.335). No sample in the two groups carries the variation of CYP21 I172N and HSD3B2 L236S.

CONCLUSION: Among these six activity SNPs in five candidate genes, IRS-1 972R was statistically associated with the onset time of puberty in Chinese girls. In order to confirm whether the candidate genes have any other activity SNPs that are associated with the onset time of puberty in Chinese girls, resequencing of these candidate genes is needed in following time....

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