Association Between Obsessive Compulsive Disorder And Tumor Necrosis Factor-Α Gene –308 (G>A) And –850 (C>T) Polymorphisms In Turkish Children

Abstract

Obsessive compulsive disorder (OCD) is a neurobiological disease characterized with obsessions and compulsions. Obsessive compulsive disorder occurs with an autoimmune mechanism after Group A β hemolytic streptococcus (GABHS) infection. Tumor necrosis factor (TNF) is an important cytokine, as well as having an important role in the apoptosis mechanism of autoimmune diseases. It is expressed by the TNF-α gene. The aim of this study was to examine the relationship between the TNF-α gene promoter region −308 (G>A) and −850 (C>T) polymorphisms and OCD. In this study, ages of the OCD patients and the control group ranged between 4 and 12 years. We studied two patient groups, one included childhood onset OCD patients (n = 49) and the control group was composed of healthy children (n = 58). Patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) criteria and with Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime (KSAD-S-PL) version. For identifying the polymorphisms, polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and polyacrylamide gel electrophoresis (PAGE) methods were used.For the −308 polymorphism, 45 of 49 OCD patients’ results were completed, and for the −850 polymorphism, 47 of 49 OCD patients’ results were completed. According to our statistical results, there is a positive relationship between OCD and the −308 polymorphism (p <0.001) but no association between OCD and the −850 polymorphism (p = 0.053). There is no positive relationship between antistreptolysin O (ASO) titers and the −308 polymorphism (p = 0.953) but there is an important significance between the −850 polymorphism and ASO (p = 0.010). There is no positive relationship between gender of patients and OCD (p = 0.180) and no positive association between ASO and gender (p = 0.467). According to our results, we hypothesize that we can propose the mutant AA genotype for the −308 polymorphism, and that the mutant CT genotype for the −850 polymorphism may be used as molecular indicators for OCD.

Tumor necrosis factor‐alpha −1031T/C polymorphism is associated with cognitive deficits in chronic schizophrenia patients versus healthy controls

“…The first finding—that TNF‐ α −1031T/C is not significantly associated with the development of schizophrenia—is consistent with two prior studies conducted on a similar Han Chinese population demonstrating that a number of TNF‐ α single nucleotide polymorphisms, such as −238G/A, −308G/A, −857C/T, and −863C/A are not more or less prevalent in schizophrenia as compared to controls (Duan et al, ; Srinivas et al, ). However, some other studies reported that TNF‐ α −308G/A allele is a risk factor for schizophrenia when examined in North Indian, Saudi, Turkish, Pakistani, and Korean populations, indicating a possible interaction between genetic background and environment (Handoko et al, ; Kadasah, Arfin, Rizvi, Al‐Asmari, & Al‐Asmari, ; Luleyap et al, ; Pae et al, ). One main explanation for this discrepancy on the association between TNF‐ α −1031T/C polymorphism and the susceptibility to schizophrenia may be due to ethnic difference, since it appears that the allele frequency of the variant allele C varied markedly from different ethnicities (Duan et al, ; Handoko et al, ; Kadasah et al, ; Luleyap et al, ; Pae et al, ; Srinivas et al, ).…”

“…However, some other studies reported that TNF‐ α −308G/A allele is a risk factor for schizophrenia when examined in North Indian, Saudi, Turkish, Pakistani, and Korean populations, indicating a possible interaction between genetic background and environment (Handoko et al, ; Kadasah, Arfin, Rizvi, Al‐Asmari, & Al‐Asmari, ; Luleyap et al, ; Pae et al, ). One main explanation for this discrepancy on the association between TNF‐ α −1031T/C polymorphism and the susceptibility to schizophrenia may be due to ethnic difference, since it appears that the allele frequency of the variant allele C varied markedly from different ethnicities (Duan et al, ; Handoko et al, ; Kadasah et al, ; Luleyap et al, ; Pae et al, ; Srinivas et al, ). The additional factors such as heterogeneity of the schizophrenia diagnosis, small gene effects, and population stratification may be also involved.…”

Association between pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections disease and tumor necrosis factor-α gene−308 g/a, −850 c/t polymorphisms in 4-12-year-old children in Adana/Turkey

“…In many multifactorial and single gene neurodegenerative disorders, the symptoms are similar, but also these are the common characteristics of polygenic traits. [45] In addition, there are symptoms which differ from patient-to-patient. For that reason, simultaneous expression profiles of immune system genes should be investigated as well.…”

Association of the tumor necrosis factor ‐308 A/G promoter polymorphism with Tourette syndrome

“…() using an extended patient population (the number of OCD cases increased from 111 to 183), whereas the association between the ‐308 A‐allele and OCD has not been verified. The ‐308 A‐allele and AA genotype, however, was much more frequent among 45 OCD patients compared to 58 controls in a Turkish study (Lüleyap et al ., ). One of the possible reasons behind the contradictory findings could be the different allele frequencies in the studied populations: the frequency of the minor ‐308 A‐allele was much lower in the Turkish and Brazilian control groups (4.3% and 9%, respectively) compared to Caucasian populations [see the CEU panel with 17.3% (http://www.ncbi.nlm.nih.gov/snp/), the Hungarian control sample with 15.2% (Table ), or the mainly Caucasian Canadian sample with 13.2% (Zai et al ., )].…”