CAG Repeats of KCNN3 Gene in the Patients with Schizophrenia / 신경정신의학

OBJECTS:We investigated a possible association between the polymorphic trinucleotide repeat(TNR) expansion in neuronal potassium channel gene KCNN3 and schizophrenia. METHODS: CAG/CTG repeat distribution in KCNN3, CTG18.1 and ERDA1 was examined and the copy number of ligation product in repeat expansion detection(RED) was measured in Korean patients with schizophrenia(n=245) and ethnically matched healthy controls(n=116). RESULTS: Longer alleles in the KCNN3 gene were over-represented in patients. The frequency of alleles with CAG repeats longer than 19 copy in the KCNN3 gene was higher in the patients with schizophrenia as compared to controls(73.3% vs. 65.1%;p=0.029, Fisher's exact test). And this difference was more prominent in schizophrenic patients with familial background(p=0.03, Fisher's exact test). We found no difference in the frequency of longer alleles between negative and positive subtypes of schizophrenia. Ligation product size in RED and alleles with CAG repeat number in the CTG18.1 gene was not increased in the patients. The copy number of ligation product in RED was highly correlated with CAG/CTG copies of ERDA1 in the patient group(r=0.45, p<0.001) as well as in the control group(r=0.44, p<0.001). However, CAG repeat length in the KCNN3 gene was not correlated with ERDA1 score. CONCLUSIONS: Our results support the hypothesis that the longer allele of KCNN3 may be considered as a candidate gene for schizophrenia, especially in the case with familial background. And the RED assay results was affected by the CAG copy number of ERDA1.

CAG Repeat Expansions in the Patients with Mood Disorder / 신경정신의학

OBJECTIVES: The genetic facotrs have been suggested for the etiology of mood disorders but the mode of inheritance is complex. Increased severity and an earlier onset of the bipolar and major depressive disorder over generations within families(Anticipation) were reported. In order to test the hypothesis that trinucleotide repeat expansions underlie the genetic basis of Bipolar and major depressive disorders, we have analyzed the extent of CAG reapeats in genomic DNA from mood disorder patients. METHODS: 55 bipolar disorder, 67 major depressive disorder patients were recruited according to the DSM-III-R criteria. 89 normal controls were recruited from the medical personnel, students and the visitors to the health services center who had no history of psychiatric illness and show normal profile of MMPI. The genomic DNA of patients and controls was analyzed by use of the(CTG) 17 oligonucleotide and the repeat expansion detection(RED) method. The Mann-Whitney U test was used to compare the distribution of the number of CAG repeats among the groups. RESULTS: when the bipolar disorder, major depressive disorder patients were compared with the control group, no significant differences were observed. CONCLUSION: Our results do not support the hypothesis that expanding CAG repeats are causing the observed genetic anticipation in bipolar disorders and major depressive disorders.