Interleukin-1 beta gene polymorphism and its interactions with neuregulin-1 gene polymorphism are associated with schizophrenia.
Interleukin-1beta (IL-1beta) and neuregulin-1 (NRG-1) have an important role in development of the central nervous system. Several recent studies suggest that their genetic polymorphisms are associated with schizophrenia. We studied the effects of the IL-1beta gene (IL-1B) -511 and NRG-1 SNP8NRG221533 polymorphisms and their interactions on the risk and age of onset of schizophrenia in 113 Finnish schizophrenic patients and 393 healthy controls. The allele and genotype frequencies of IL-1B and NRG-1 did not differ between schizophrenic patients and healthy controls, but the risk of schizophrenia was more than 10 times higher (odds ratio 10.20, 95% CI 2.53-41.09, p = 0.001) among subjects with the IL-1B 2.2, NRG-1 CC genotypes compared to subjects with the IL-1B 2.2, NRG-1 T-allele carriage. There was also a trend for an association between the interaction between IL-1B and NRG-1 polymorphisms and the age at onset of schizophrenia (chi(2) = 2.80; df = 1; p = 0.09, log rank test). IL-1B-511 allele 1 homozygotes had a significantly higher age of onset than allele 2 carriers (mean age of onset 25.9 +/- 7.7 and 22.7 +/- 5.4 years, t-test: t = 2.46; p = 0.032). Our results suggest that there is an interaction between the IL-1B and NRG-1 genes in schizophrenia. In addition, the IL-1B-511 polymorphism seems to be associated with the age at onset of schizophrenia.
Hänninen
Kari
K
Dept. of Psychiatry, South Karelia Central Hospital, Valto Käkelän katu 14 C/6, Lappeenranta 53130, Finland. kari.hanninen@ekshp.fi
Katila
Heikki
H
Saarela
Marika
M
Rontu
Riikka
R
Mattila
Kari M
KM
Fan
Meng
M
Hurme
Mikko
M
Lehtimäki
Terho
T
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D020890:Neuregulin-1 / Q000235:genetics* / Q000502:physiology*; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D012306:Risk; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D016019:Survival Analysis
D053583:Interleukin-1beta; D020890:Neuregulin-1