ABSTRACT
OBJECTIVES: Neurotensin (NT), of which functions are evoked by its interaction with neurotensin receptors (NTR), coexists with mesolimbic dopamine and regulates endogenous dopamine release. Recent studies have shown that NT with NTR exerts neuroleptic-like activity within the central nervous system and may play an important role in the pathogenesis and in the treatment of schizophrenia. We have examined the genetic association between schizophrenia and tetranucleotide repeat polymorphism in the 3'-flanking region of the NTR gene to investigate the possible contribution of the NTR gene to the schizophrenia susceptibility. METHODS: Among 23 alleles identified, the subjects were 120 patients (male 91, female 29) with schizophrenia and 106 normal healthy controls (male 84, female 22). They were unrelated native Korean. PANSS was used to determine positive or negative subgroup in the schizophrenic patients.Using polymerase chain reaction and polyacrylamide gel electrophoresis, tetranucleotide repeat polymorphism (CCTT and CTTT) in the 3'-flanking region of NTR gene was observed. For a comparison of NTR gene's allelic frequencies between patients with schizophrenia and normal healthy controls, chi-square test and Bonferroni's correction was performed. RESULTS: The frequency of A10 allele (base pair size=399) was significantly higher in normal healthy controls than schizophrenia (x2=16.4902, df=1, p<.000). In the comparison between schizophrenic patients with negative symptoms and normal controls, the frequency of A10 allele was significantly higher in normal healthy control subjects than patients with schizophrenia (x2=21.33, df=1, p<0.001). In the case of male, the frequency of A10 allele of schizophrenia was significantly higher than normal controls (x2=13.71, df=1, p<0.001). CONCLUSIONS: NTR gene was negatively associated with schizophrenia. NTR gene's tetranucleotide repeat polymorphism may provide some protective function against schizophrenia.