• Association between 15 insertion/deletion genetic polymorphisms and risk of schizophrenia using pooled samples
  • Maedeh Bordbar,1,* Mostafa Saadat,2
    1. Department of Biology, College of Sciences, Shiraz University
    2. Department of Biology, College of Sciences, Shiraz University


  • Introduction: Schizophrenia is a psychiatric syndrome that affects approximately 1% of the world population and is among the top 10 reasons for disability. Genome-wide association studies showed that multiple common variants, each with small effect, are associated with schizophrenia. More than 100 loci are significantly associated with schizophrenia. In this case-control study, we investigated the association between 15 insertion/deletion (Indel) polymorphisms in APOB, ADRA2B, PDCD6IP, LRPAP1, TLR2, DHFR, VEGF, HLA-G, TPA, DBH, UCP2, FADS2, MDM2, TP53, SLC6A4 genes and schizophrenia risk using pooled samples. DNA pooling is a well-established method for reducing the cost and effort of large-scale association studies. DNA pooling combines DNA from numerous persons into a single sample which can be genotyped just once, instead of genotyping every individual.
  • Methods: In the present case-control study, 361 individuals with schizophrenia and 360 healthy individuals were included in the study. Genomic DNA was extracted from blood samples by boiling method. Two pooled samples (healthy control and schizophrenia groups) were prepared by mixing of equal amounts of extracted genomic DNA. PCR was used to determine the allele frequency of each polymorphism. The band intensity, which has been measured with ImageJ software, has high level of accuracy as an indicator for determining the relative amounts of DNA.
  • Results: The results showed that the Del alleles of HLA-G 14bp Indel (OR=1.23, 95% CI=1.01-1.52, p=0.045) and the TPA 300bp Indel (OR=0.67, 95% CI=0.54-0.82, p<0.001) had a significant association with the risk of schizophrenia. However, significant differences were not observed in the other insertion/deletion polymorphisms studied in this research.
  • Conclusion: There is no study on TPA 300bp Indel polymorphism and risk of schizophrenia, but previous studies showed that abnormal function of TPA is related to the pathogenesis of schizophrenia and tPA actively participates in the mechanisms of neurogenesis and angiogenesis, which might justify not only the impaired neurogenesis but also the low prevalence of neoplastic diseases among schizophrenics. The present study shows that the insertion allele is associated with an increased risk of schizophrenia. HLA-G 14bp Indel is associated with HLA-G expression and function. This genetic variant also influences brain morphometric measures and HLA-G could be an important biomarker for schizophrenia. Further, low levels of sHLA-G were shown to have a significant impact on Clinical Global Impression (CGI) severity in people with schizophrenia. Our study demonstrates that the deletion allele is associated with an increased risk of schizophrenia. Future case-control genetic association studies are needed to conclude that these polymorphisms are risk factors for schizophrenia.
  • Keywords: Insertion/deletion polymorphisms, Schizophrenia, Pooled samples, personalized medicine