Association Study of Single-Nucleotide Polymorphism in Lymphotoxin Alpha Gene and Bipolar I Disorder

ABSTRACT

OBJECTIVES: Proinflammatory process has been implicated as an underlying mechanism of bipolar disorder and schizophrenia. Previous studies have suggested a possible role of lymphotoxin alpha (LTA) gene in the development of schizophrenia and have prompted further investigation in bipolar patients. Association of the LTA +252A/G polymorphism with susceptibility to bipolar I disorder itself as well as with vulnerability among a subset of psychotic bipolar patients were tested. METHODS: DNA extraction was done by a standard method and genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 114 Korean patients with bipolar I disorder and 202 healthy controls. SPSS v18.0 was used for statistical analysis. Comparisons of the genotype and allele distributions in LTA +252A/G polymorphism were made using a chi-square test. The genotype and allele associations were also evaluated using odds ratio (OR) and 95% confidence interval (CI). Statistical significance was accepted when p was < 0.05. RESULTS: No significant association was found between the LTA +252A/G polymorphism and bipolar disorder. However, LTA +252G allele was present with significantly higher frequency among bipolar patients with psychotic features compared to those without (chi2 = 4.69, p = 0.034, OR = 2.495, 95% CI = 1.069-5.827). CONCLUSION: The results suggest that the allele LTA +252G of the polymorphism may be associated with the psychotic subset of bipolar disorder but not with bipolar I disorder itself. Adequately powered subsequent studies should be conducted.