Tumor Necrosis Factor-α and -β Genetic Polymorphisms As a Risk Factor in Saudi Patients with Schizophrenia

Overview

Journal Neuropsychiatr Dis Treat

Publisher Dove Medical Press

Specialty Psychiatry

Date 2017 Apr 27

PMID 28442912

Citations 8

Authors

Saeed Kadasah

Misbahul Arfin

Sadaf Rizvi

Mohammed Al-Asmari

Abdulrahman Al-Asmari

Affiliations

Soon will be listed here.

Abstract

Background: Schizophrenia is one of the most common devastating psychiatric disorders that negatively affects the quality of life and psychosocial functions. Its etiology involves the interplay of complex polygenic influences and environmental risk factors. Inflammatory markers are well-known etiological factors for psychiatric disorders, including schizophrenia.

Objective: The aim of this study was to investigate the association of proinflammatory cytokine genes, tumor necrosis factor (TNF)-α (-308G/A) and TNF-β (+252A/G) polymorphisms with schizophrenia susceptibility.

Subjects And Methods: and genes were amplified using amplification refractory mutation system primers in 180 schizophrenia patients and 200 healthy matched controls recruited from the Psychiatry Clinic of Prince Sultan Military Medical City, Riyadh. The frequencies of alleles and genotypes of TNF-α (-308G/A) and TNF-β (+252A/G) polymorphisms in patients were compared with those in controls.

Results: The frequencies of TNF-α (-308) allele A and genotype GA were significantly higher, while those of allele G and genotype GG were lower in schizophrenia patients as compared to controls, indicating that genotype GA and allele A of TNF-α (-308G/A) may increase susceptibility to schizophrenia, while genotype GG and allele G may reduce it. On the other hand, the distribution of alleles and genotypes of TNF-β (+252A/G) polymorphism does not differ significantly in patients from controls; however, the frequency of genotype GG of TNF-β (+252A/G) was significantly higher in male patients than in female patients. The distribution of TNF-α (-308G/A) and TNF-β (+252A/G) polymorphisms was almost similar in schizophrenia patients with negative or positive symptoms.

Conclusion: TNF-α (-308G/A) and TNF-β (+252G/A) polymorphisms may increase the susceptibility to schizophrenia in Saudi patients and could be a potential risk factor for its etiopathogenesis. However, further studies are warranted involving a larger sample size to strengthen our findings.

Citing Articles

Mendelian randomization analysis of causal and druggable circulating inflammatory proteins in schizophrenia.

Cao H, Fu L, Liu D, Baranova A, Zhang F Front Psychiatry. 2024; 15:1465291.

PMID: 39544374 PMC: 11560794. DOI: 10.3389/fpsyt.2024.1465291.

Microglia and cognitive impairment in schizophrenia: translating scientific progress into novel therapeutic interventions.

Zhuo C, Tian H, Song X, Jiang D, Chen G, Cai Z Schizophrenia (Heidelb). 2023; 9(1):42.

PMID: 37429882 PMC: 10333203. DOI: 10.1038/s41537-023-00370-z.

Role of TNF-α -308G/A Polymorphism in Bipolar Disorder and its Relationship with Clinical and Demographic Variables.

Akram S, Ali M, Mutahir Z, Ibad N, Sarmad S, Mehboob S Innov Clin Neurosci. 2023; 20(1-3):60-71.

PMID: 37122575 PMC: 10132278.

Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review.

de Bartolomeis A, Barone A, Vellucci L, Mazza B, Austin M, Iasevoli F Mol Neurobiol. 2022; 59(10):6460-6501.

PMID: 35963926 PMC: 9463235. DOI: 10.1007/s12035-022-02976-3.

Glial changes in schizophrenia: Genetic and epigenetic approach.

Francisco R, Fernando V, Norma E, Madai M, Marcelo B Indian J Psychiatry. 2022; 64(1):3-12.

PMID: 35400734 PMC: 8992743. DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_104_21.

References

Shi J, Gershon E, Liu C . Genetic associations with schizophrenia: meta-analyses of 12 candidate genes. Schizophr Res. 2008; 104(1-3):96-107. PMC: 2562556. DOI: 10.1016/j.schres.2008.06.016. View

Abraham L, Kroeger K . Impact of the -308 TNF promoter polymorphism on the transcriptional regulation of the TNF gene: relevance to disease. J Leukoc Biol. 1999; 66(4):562-6. DOI: 10.1002/jlb.66.4.562. View

Wilson A, Symons J, McDowell T, McDevitt H, Duff G . Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci U S A. 1997; 94(7):3195-9. PMC: 20345. DOI: 10.1073/pnas.94.7.3195. View

Schwarz M, Muller N, Riedel M, Ackenheil M . The Th2-hypothesis of schizophrenia: a strategy to identify a subgroup of schizophrenia caused by immune mechanisms. Med Hypotheses. 2001; 56(4):483-6. DOI: 10.1054/mehy.2000.1203. View

Srinivas L, Vellichirammal N, Alex A, Nair C, Nair I, Banerjee M . Pro-inflammatory cytokines and their epistatic interactions in genetic susceptibility to schizophrenia. J Neuroinflammation. 2016; 13(1):105. PMC: 4866417. DOI: 10.1186/s12974-016-0569-8. View

Ashdown H, Dumont Y, Ng M, Poole S, Boksa P, Luheshi G . The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia. Mol Psychiatry. 2005; 11(1):47-55. DOI: 10.1038/sj.mp.4001748. View

Allen N, Bagade S, McQueen M, Ioannidis J, Kavvoura F, Khoury M . Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nat Genet. 2008; 40(7):827-34. DOI: 10.1038/ng.171. View

Lv M, Tan Y, Yan S, Tian L, Chen D, Tan S . Decreased serum TNF-alpha levels in chronic schizophrenia patients on long-term antipsychotics: correlation with psychopathology and cognition. Psychopharmacology (Berl). 2014; 232(1):165-72. DOI: 10.1007/s00213-014-3650-y. View

Beutler B, Cerami A . The biology of cachectin/TNF--a primary mediator of the host response. Annu Rev Immunol. 1989; 7:625-55. DOI: 10.1146/annurev.iy.07.040189.003205. View

10.

Riedel M, Kronig H, Schwarz M, Engel R, Kuhn K, Sikorski C . No association between the G308A polymorphism of the tumor necrosis factor-alpha gene and schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2002; 252(5):232-4. DOI: 10.1007/s00406-002-0386-1. View

11.

Tsai S, Hong C, Yu Y, Lin C, Liu L . No association of tumor necrosis factor alpha gene polymorphisms with schizophrenia or response to clozapine. Schizophr Res. 2003; 65(1):27-32. DOI: 10.1016/s0920-9964(02)00531-5. View

12.

Kronfol Z, Remick D . Cytokines and the brain: implications for clinical psychiatry. Am J Psychiatry. 2000; 157(5):683-94. DOI: 10.1176/appi.ajp.157.5.683. View

13.

Muller N, Riedel M, Ackenheil M, Schwarz M . Cellular and humoral immune system in schizophrenia: a conceptual re-evaluation. World J Biol Psychiatry. 2003; 1(4):173-9. DOI: 10.3109/15622970009150588. View

14.

Watanabe Y, Muratake T, Kaneko N, Fukui N, Nara Y, Someya T . No association between the tumor necrosis factor-alpha gene promoter polymorphisms and schizophrenia in a Japanese population. Psychiatry Res. 2007; 153(1):1-6. DOI: 10.1016/j.psychres.2006.03.009. View

15.

Al-Harthi F, Zouman A, Arfin M, Tariq M, Al-Asmari A . Tumor necrosis factor-α and -β genetic polymorphisms as a risk factor in Saudi patients with vitiligo. Genet Mol Res. 2013; 12(3):2196-204. DOI: 10.4238/2013.July.8.1. View

16.

Hudson Z, Miller B . Meta-Analysis of Cytokine and Chemokine Genes in Schizophrenia. Clin Schizophr Relat Psychoses. 2016; 12(3):121-129B. DOI: 10.3371/CSRP.HUMI.070516. View

17.

Morar B, Schwab S, Albus M, Maier W, Lerer B, Wildenauer D . Evaluation of association of SNPs in the TNF alpha gene region with schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2006; 144B(3):318-24. DOI: 10.1002/ajmg.b.30451. View

18.

Zai G, Muller D, Volavka J, Czobor P, Lieberman J, Meltzer H . Family and case-control association study of the tumor necrosis factor-alpha (TNF-alpha) gene with schizophrenia and response to antipsychotic medication. Psychopharmacology (Berl). 2006; 188(2):171-82. DOI: 10.1007/s00213-006-0482-4. View

19.

Al-Rayes H, Al-Swailem R, Albelawi M, Arfin M, Al-Asmari A, Tariq M . TNF-α and TNF-β Gene Polymorphism in Saudi Rheumatoid Arthritis Patients. Clin Med Insights Arthritis Musculoskelet Disord. 2011; 4:55-63. PMC: 3140274. DOI: 10.4137/CMAMD.S6941. View

20.

Meira-Lima I, Pereira A, Mota G, Floriano M, Araujo F, Mansur A . Analysis of a polymorphism in the promoter region of the tumor necrosis factor alpha gene in schizophrenia and bipolar disorder: further support for an association with schizophrenia. Mol Psychiatry. 2003; 8(8):718-20. DOI: 10.1038/sj.mp.4001309. View