Association of tumor necrosis factor alpha gene -G308A polymorphism with schizophrenia.
BACKGROUND
Tumor necrosis factor alpha (TNFalpha), a cytokine involved in inflammatory processes, has been implicated in the pathophysiology of schizophrenia. The chromosomal location in the major histocompatibility complex (MHC) region on 6p21.1-21.3, a region with evidence for linkage, suggests a role in susceptibility to schizophrenia. Association of the minor (A) allele of the -G308A TNFalpha gene polymorphism with schizophrenia has been reported [Mol. Psychiatry 6 (2001) 79].


METHODS
Association of the -G308A TNFalpha gene and the lymphotoxin alpha (LTalpha)+A252G gene polymorphisms with schizophrenia was studied in 79 sib pair families with linkage in the MHC region and in 128 trio families using the transmission disequilibrium test (TDT).


RESULTS
Weak association of the common G allele was detected for TNFalpha -G308A in both samples independently with borderline significance in the sib pair families (0.064) and with a nominally significant value of P=0.022 in the trio families. Combining both samples produced P=0.003, while LTalpha+A252G, located approximately 2-3 kb distally, revealed P=0.03 and the two locus haplotype yielded a P value of 0.001.


CONCLUSIONS
Our data suggests association of the common G allele of the -G308A TNFalpha gene polymorphism with schizophrenia in a sample of 207 families. However, linkage disequilibrium with a different allele of the TNFalpha gene or another gene in the MHC region cannot be excluded.
Schwab
Sibylle G
SG
Department of Psychiatry, University of Bonn, Wilhelmstr. 31, D-53111 Bonn, Germany.
Mondabon
Stephanie
S
Knapp
Michael
M
Albus
Margot
M
Hallmayer
Joachim
J
Borrmann-Hassenbach
Margitta
M
Trixler
Matyas
M
Gross
Magdalena
M
Schulze
Thomas G
TG
Rietschel
Marcella
M
Lerer
Bernard
B
Maier
Wolfgang
W
Wildenauer
Dieter B
DB
D000483:Alleles; D002896:Chromosomes, Human, Pair 6; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008233:Lymphotoxin-alpha / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000235:genetics; D008957:Models, Genetic; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D012565:Schizophrenic Psychology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha