Association between Schizophrenia and the Genetic Polymorphism of DRD3, DRD4 and HTR2A.
- Author:
Na Young HWANG
1
;
Kyu Wol YUN
;
Yeon Ho JOO
;
Chang Yoon KIM
;
Suk Hoon JUNG
;
Byungsu KIM
;
Eun Soon SHIN
;
Sun Young OH
;
Heung Bum OH
Author Information
1. Department of Neuropsychiatry, College of Medicine, Ewha Womans University, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Schizophrenia;
DRD3;
DRD4;
HTR2A;
Association study;
Gene interaction
- MeSH:
Age of Onset;
Alleles;
Dopamine;
Electrophoresis;
Female;
Gene Frequency;
Genetic Load;
Genotype;
Humans;
Linear Models;
Male;
Phenotype;
Polymerase Chain Reaction;
Polymorphism, Genetic*;
Receptors, Serotonin;
Schizophrenia*
- From:The Korean Journal of Laboratory Medicine
2004;24(6):446-451
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Dopamine and serotonin receptors are candidate genes for the genetic study of schizophrenia because of their implication in the pathophysiology and etiology of schizophrenia (serotonine- dopamin hypothesis). A population-based association study was performed between schizophrenics and normal controls to identify the susceptibility genes. METHODS: A total of 145 schizophrenics and 242 normal controls were recruited. Ser9Gly polymorphism of DRD3, 12 bp repeat of DRD4, and 102T/C of HTR2A were selected as candidate polymorphism. The molecular techniques such as polymerase chain reaction (PCR)-restriction fragment length polymorphism and PCR-polyacrylamide gel electrophoresis were used. Chi-square analysis was performed to find any differences between two groups and logistic linear regression was tested to evaluate the interaction between three genes. RESULTS: There were no significant differences in allele frequencies and genotype frequencies of the three genetic polymorphism. Stratified by sex, the difference of DRD4 allele (P=0.065) and HTR2A allele (P=0.083) and genotype (P=0.054) was observed between male patients and controls; also noted was the difference of HTR2A genotype (P=0.080) between female patients and controls. Stratified by age of onset, the difference in the linear trend of DRD3 between early-onset patients and normal control (P=0.003) was observed. Stratified by family history, the difference in the linear trend of DRD4 (P=0.008) was also observed. Logistic linear regression with 90 patients who had early-onset phenotype (< or =20 year-old) or family history showed a significant result in interaction term (P=0.053). CONCLUSIONS: The finding that there were significant results only after stratification may imply a different genetic load on each subgroup of the disease. The interaction of genes between DRD3, DRD4, and HTR2A in a subgroup with supposedly high genetic background may support the serotonindopamine hypothesis. This, however, should be verified hereafter in large-scale studies.
