VNTR Polymorphism of the Tyrosine Hydroxylase in Bipolar Patients

Kweon, Yong Sil; Toh, Kyu Young; Jun, Tae Youn; Paik, In Ho

Abstract

OBJECTIVES
Tyrosine hydroxylase(TH) is a rate-limiting enzyme in the synthesis of catecholamines, and could be a candidate gene for causing the bipolar disorders. Therefore, we designed this study to investigate the association of the VNTR(variable number of tandem repeats) polymorphic locus in the first intron of the TH gene with bipolar disorders.
METHODS
We typed VNTB polymorphic region of the TH gene using PCR in 115 bipolar patients and 85 normal controls. Four types of alleles(A, B, C, D) were typed according to the difference of the repeat(TCAT)6-9 number. The frequencies of allele and genotype were compared between patients and normal controls, and in patients and normal controls allelic frequencies were compared respectively in terms of family history of affective disorders and age of onset.
RESULTS
1) The allelic frequencies were significantly lower in type A, and significantly higher in type D in patient group compared to control group. The genotype frequencies were significantly higher in type BD in patient group than in control group. 2) In comparing the allelic frequencies among patient group with and without family history and control group, there were no significant differences between groups with and without family history, whereas patient group with family history showed lower significance in type A and higher significance in type D compared to control group. 3) In comparing the allelic frequencies among patient groups with early onset and late onset and control group, patient group with early onset showed higher significance in type D than patient group with late onset and showed lower significance in type A and higher significance in type D compared to control group.
CONCLUSIONS
The authors conclude that the VNTR polymorphic region of the TH gene might be associated bipolar disorders, and type A and type D alleles might be susceptibility genes of bipolar disorder.