Association of tumor necrosis factor -308G/A promoter polymorphism with schizophrenia and bipolar affective disorder in a Polish population.
OBJECTIVE
Schizophrenia (SCH) and bipolar affective disorder (BPAD) are complex disorders with significant participation of genetic risk factors. Several lines of evidence point to the role of shared neurobiological mechanisms and common genetic background in SCH and BPAD. Immune disturbances have been suggested as contributing factor in the pathogenesis of both SCH and BPAD. The gene coding cytokine tumor necrosis factor (TNF) has been the object of a number of association studies in SCH, with ambiguous results. Only 3 such studies were performed in BPAD. The aim of our study was to perform a case-control association analysis of the TNF -308G/A polymorphism in a Polish sample of patients with SCH, BPAD and healthy controls.


METHODS
We genotyped the TNF -308G/A polymorphism (rs1800629) by PCR-RFLP in 348 patients with SCH, 361 patients with BPAD and in 351 controls.


RESULTS
We observed an association of the -308G allele with both SCH (p = 0.008) and BPAD (p = 0.039), and also with a positive family history in patients with SCH (p = 0.048) and BPAD (p = 0.027). For TNF genotypes, the association was only seen in SCH (p = 0.018).


CONCLUSIONS
Our results may point to an association of the TNF -308G allele and -308G/G genotype with both SCH and BPAD, and to a relationship of the -308G allele with the risk of SCH and BPAD in patients with a positive family history. TNF could be potentially a susceptibility gene, shared between SCH and BPAD. Complex TNF gene studies--based on multiple single-nucleotide polymorphisms and involving haplotype analysis--are necessary for the clarification of currently contradictory findings.
Czerski
Piotr M
PM
Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland. pczerski@amp.edu.pl
Rybakowski
Filip
F
Kapelski
Paweł
P
Rybakowski
Janusz K
JK
Dmitrzak-Weglarz
Monika
M
Leszczyńska-Rodziewicz
Anna
A
Słopień
Agnieszka
A
Skibińska
Maria
M
Kaczmarkiewicz-Fass
Magdalena
M
Hauser
Joanna
J
D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011044:Poland / Q000453:epidemiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence; D012559:Schizophrenia / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D011795:Surveys and Questionnaires; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha