engleski

Association of Tagging Single Nucleotide Polymorphisms (SNPs) on Eight Candidate Genes in the Dopaminergic pathway with Schizophrenia in Croatian Population

Aim: To perform a comprehensive evaluation of association of common genetic variants in candidate genes in the dopaminergic pathway with schizophrenia in a sample from Croatian population. Methods: A case-control association study was performed on 104 unrelated schizophrenia cases recruited in a psychiatric hospital in Zagreb and 131 phenotypically normal Croatian subjects. Forty-nine tagging SNPs (tagSNPs) in eight candidate genes in the dopaminergic pathway were identified from the HapMap database and tested for association. Genotyping was performed using the SNPlex platform. Statistical analysis was conducted to assess allelic and genotypic associations between cases and controls using a goodness of fit &#967; 2 test and trend test, respectively ; adjustment for multiple testing was done by permutation based analysis. Results: Significant allele frequency differences between schizophrenia cases and normal controls were observed at four tagSNPs located in the genes DRD5, HTR1B1, DBH, TH1 (p<0.01). A trend test also confirmed the genotypic association (p<0.01) of these four tagSNPs. Additionally, moderate association (p<0.05) was observed with eight tagSNPs on SLC6A3, DBH, DRD4, SLC6A4 and COMT. Conclusions: This study establishes that common genetic variants in genes involved in the dopaminergic pathway influence susceptibility to schizophrenia in populations of Caucasian descent.

Schizophrenia; candidate genes; dopamine pathway; tagging SNPs; allelic association; Croatian population

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