Polymorphic CA repeat in IGF-I gene: lack of association with schizophrenia

Bonvicini, Cristian; Gennarelli, Massimo; Scassellati, Catia; Bignotti, Stefano; Gardella, Rita; Barlati, Sergio; Valsecchi, Paolo; Sacchetti, Emilio

doi:10.1097/ypg.0b013e3283351167

Cited by 4 publications

(3 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with our other recent reports [32], [33], to be eligible, both patients and controls had to be white and of Italian descent for at least 2 generations, have no relatives among other prospective participants, have given written informed consent, and fulfil predefined group-specific inclusion and exclusion criteria.…”

Section: Methodsmentioning

confidence: 56%

New Copy Number Variations in Schizophrenia

et al. 2010

Self Cite

View full text Add to dashboard Cite

Genome-wide screenings for copy number variations (CNVs) in patients with schizophrenia have demonstrated the presence of several CNVs that increase the risk of developing the disease and a growing number of large rare CNVs; the contribution of these rare CNVs to schizophrenia remains unknown. Using Affymetrix 6.0 arrays, we undertook a systematic search for CNVs in 172 patients with schizophrenia and 160 healthy controls, all of Italian origin, with the aim of confirming previously identified loci and identifying novel schizophrenia susceptibility genes. We found five patients with a CNV occurring in one of the regions most convincingly implicated as risk factors for schizophrenia: NRXN1 and the 16p13.1 regions were found to be deleted in single patients and 15q11.2 in 2 patients, whereas the 15q13.3 region was duplicated in one patient. Furthermore, we found three distinct patients with CNVs in 2q12.2, 3q29 and 17p12 loci, respectively. These loci were previously reported to be deleted or duplicated in patients with schizophrenia but were never formally associated with the disease. We found 5 large CNVs (>900 kb) in 4q32, 5q14.3, 8q23.3, 11q25 and 17q12 in five different patients that could include some new candidate schizophrenia susceptibility genes. In conclusion, the identification of previously reported CNVs and of new, rare, large CNVs further supports a model of schizophrenia that includes the effect of multiple, rare, highly penetrant variants.

show abstract

Section: Methodsmentioning

confidence: 56%

New Copy Number Variations in Schizophrenia

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…Similarly, single nucleotide polymorphism and variable number tandem repeat polymorphism studies support the conclusion that the IGF-1 gene is not involved in schizophrenia (Bonvicini et al, 2010;Gunnell et al, 2007). It should also be noted that peripheral IGF-1 levels may be influenced by a range of factors, such as age, gender, diet, physical activity, BMI, ethnicity, growth hormone, thyroid and parathyroid hormones, cortisol, insulin, estrogens, androgens, inflammatory cytokines, kidney and liver function, diabetic status, and genetic factors (Chanson et al, 2016;Demirel et al, 2014;Frystyk et al, 2010;Gunnell et al, 2007).…”

Section: Discussionmentioning

confidence: 77%

Meta‐analysis of peripheral insulin‐like growth factor 1 levels in schizophrenia

et al. 2022

View full text Add to dashboard Cite

Objective We aimed to investigate if there is a significant difference in peripheral insulin‐like growth factor 1 (IGF‐1) levels between schizophrenia patients and healthy controls and to determine whether a difference exists before and after initiation of antipsychotics. Methods PubMed/MEDLINE, Scopus, and Web of Science were searched up to March 27, 2022. Original clinical studies of any type that reported peripheral blood, serum or plasma IGF‐1 levels measured after fasting in schizophrenia patients and/or healthy control group were selected based on inclusion and exclusion criteria. Data were analyzed using Meta‐Essentials: Workbooks for meta‐analysis and pooled through random‐effects meta‐analyses. Results Twelve publications met eligibility criteria. Schizophrenia patients under antipsychotic treatment had significantly lower peripheral IGF‐1 levels compared to healthy controls (n = 632, Hedges’ g –0.42, 95% CI from –0.79 to –0.04, p = .006, I2 = 70.38%), while no significant difference was found between schizophrenia patients regardless of the antipsychotic treatment status and healthy controls, as well as between antipsychotic naïve or free schizophrenia patients and healthy controls, and before and after initiation of antipsychotic treatment. However, high heterogeneity was observed and its potential sources in some of the subgroup analyses included sample type and region. Conclusions Schizophrenia patients under antipsychotic treatment seem to have lower peripheral IGF‐1 levels compared to healthy controls. Additional studies with larger and more homogenous samples are needed to confirm these findings.

show abstract

“…Insulin resistance with brain insulin receptor deficits/receptor dysfunction was re-ported in SCZ. IDE cleaves IGF-I and IGF-II, which are implicated in the pathophysiology of SCZ, although polymorphic CA repeat in IGF1 did not show association with SCZ [174]. Brain gamma-endorphin levels, liberated from beta-endorphin exclusively by IDE, have been reported to be altered in SCZ.…”

Section: Nmdar (N-methyl D-aspartate (Nmda) Receptor; Grin1mentioning

confidence: 91%

Genomics of schizophrenia and pharmacogenomics of antipsychotic drugs

Cacabelos¹,

Cacabelos²,

Aliev³

2013

OJPsych

View full text Add to dashboard Cite

Antipsychotic drugs are the neuroleptics currently used in the treatment of schizophrenia (SCZ) and psychotic disorders. SCZ has a heritability estimated at 70% - 90%; and pharmacogenomics accounts for 60% - 90% variability in the pharmacokinetics and pharmacodynamics of psychotropic drugs. Personalized therapeutics based on individual genomic profiles in SCZ entails the characterization of 5 types of gene clusters and their related metabolomic profiles: 1) genes associated with disease pathogenesis; 2) genes associated with the mechanism of action of drugs; 3) genes associated with drug metabolism (phase I and II reactions); 4) genes associated with drug transporters; and 5) pleiotropic genes involved in multifaceted cascades and metabolic reactions. Genetic studies in SCZ have revealed the presence of chromosome anomalies, copy number variants, multiple single-nucleotide polymorphisms of susceptibility distributed across the human genome, aberrant single-nucleotide polymorphisms in microRNA genes, mitochondrial DNA mutations, and epigenetic phenomena. Pharmacogenetic studies of psychotropic drug response have focused on determining the relationship between variation in specific candidate genes and the positive and adverse effects of drug treatment. Approximately 18% of neuroleptics are major substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4. About 10% - 20% of Western populations are defective in genes of the CYP superfamily. Only 26% of Southern Europeans are pure extensive metabolizers for the trigenic cluster integrated by the CYP2D6 + CYP2C19 + CYP2C9 genes. Efficacy and safety issues in the pharmacological treatment of SCZ are directly linked to genetic clusters involved in the pharmacogenomics of antipsychotic drugs and also to environmental factors. Consequently, the incorporation of pharmacogenomic procedures both to drugs under development and drugs on the market would help to optimize therapeutics in SCZ and other central nervous system disorders.

show abstract

Polymorphic CA repeat in IGF-I gene: lack of association with schizophrenia

Cited by 4 publications

References 16 publications

New Copy Number Variations in Schizophrenia

New Copy Number Variations in Schizophrenia

Meta‐analysis of peripheral insulin‐like growth factor 1 levels in schizophrenia

Genomics of schizophrenia and pharmacogenomics of antipsychotic drugs

Contact Info

Product

Resources

About