Association study of rs11038167, rs11038172 and rs835784 of the TSPAN18 gene in Iranian schizophrenia patients

Association study of rs11038167, rs11038172 and rs835784 of the TSPAN18 gene in Iranian schizophrenia patients
Yousef Daneshmandpour ,¹ Parisa Moeinian ,² Zahra Bahmanpour ,³ Hossein Ghahramani Almanghadim ,⁴ Somayeh Kazeminasab,⁵ Babak Emamalizadeh,^6,*
1. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
2. Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
3. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
4. Department of Molecular Genetics, Faculty of Basic Sciences, Islamic Azad University, Ahar Branch,Ahar, Iran
5. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
6. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Introduction: Schizophrenia is a chronic mental disorder that affects about one percent of the world’s population. The disease is mainly characterized by delusions, hallucinations, and cognitive deficits. While hundreds of family-based and twin-based studies have confirmed the high heritability of this disorder, yet the precise molecular mechanisms regulating the pathways triggering SCZ and the cause of the disorder remains unknown. Large-scale genome-wide association studies (GWAS) have introduced putative chromosome loci suggesting potential variants of small effect which cumulatively may provide helpful clues about the etiology of SCZ. In a recent GWA study, we aimed to offer a conclusive association between the risk of schizophrenia and three single nucleotide polymorphisms (SNPs) in the Iranian population. These SNPs are located within the intronic region of the TSPAN18 gene, rs11038167, rs11038172 and rs835784. However, the results across the following replication studies are inconsistent.
Methods: This study was performed on a total of 997 individuals comprising 496 SCZ patients and 501 healthy controls, all of the Iranian descent. The two groups had no significant differences in distributions of age and gender (p > .05). Genomic DNA was extracted from the peripheral blood of 496 SZ patients and 501 healthy controls. Genomic DNA was extracted via the salting-out technique from the peripheral blood of all subjects. Rs11038167, rs11038172, and rs835784 were genotyped using the PCR-RFLP method in all subjects. Association of the genotyped SNPs and SZ were tested using the chi-squared test and logistic regression models. Pearson's chi-squared tests were applied to test for significance in differences between genotype and allele frequencies between the two groups and also to assess any deviation from the Hardy–Weinberg equilibrium. The difference between genotypes in the two cases and control groups was further assessed under log additive, recessive, and dominant genetic models using SNPassoc package of R software.
Results: The mean age of the SCZ patients and control subjects was 43.34 ± 7.21 and 44.11 ± 8.84 years, respectively. The age of onset of the disease among patients was 33 ± 1.6 years with almost 8 ± 0.03 years of illness. Patients were comprised of 350 males and 146 females and the control subjects included 343 males and 158 females. We have found significant differences in allele frequencies of the rs11038167 and rs835784 polymorphisms and also in genotype distributions of all three SNPs. The A allele of the rs11038167 and rs835784 in addition to the AA genotype of the three polymorphisms was associated with increased susceptibility to schizophrenia.
Conclusion: These results confirm the significant association between rs11038167 and rs835784 and rs11038172 polymorphisms and increased risk of schizophrenia in the Iranian population suggested earlier in previous studies on the Han Chinese population. Further replication studies designed on a larger scale on the same and other populations are required to confirm the present findings. Functional explorations are desired to focus on measuring the degree of expression and precise localization of TSPAN18 in various brain regions. Also, the analysis of the dynamics of the protein product and its potential partners, as well as the profound understanding of how downstream possible enzymatic signaling transduction is regulated by TSPAN18 is required.
Keywords: Single nucleotide polymorphism; Schizophrenia; TSPAN18; Association