Association of genetic polymorphisms in the type II deiodinase gene with bipolar disorder in a subset of Chinese population

Abstract

Objective Genetic factors play a critical role in the etiology of bipolar disorder (BPAD). Previous studies suggested an association between thyroid dysfunction and BPAD. We hypothesize that genetic variations in the type II deiodinase (DIO2) gene that possibly alter the bioactivity of thyroid hormones are associated with BPAD. Method A case–control association study was conducted in a subset of Chinese Han population. Two single nucleotide polymorphisms (SNP), open reading frame a (ORFa)-Gly3Asp (rs12885300) and Thr92Ala (rs225014) with potential functions on the activity of DIO2, were selected. The frequencies of allele, genotype and haplotype of the two SNPs were compared between the BPAD patients and the control group. Results Statistical significance between the BPAD patients and the control group was observed for the allele ( χ 2 = 7.746, P = 0.005, df = 1) and genotype frequencies ( χ 2 = 8.158, P = 0.017, df = 2) at the locus of ORFa-Gly3Asp, and for the allele ( χ 2 = 15.838, P = 7.00e−005, df = 1) and genotype frequencies ( χ 2 = 17.236, P = 0.0002, df = 2) at Thr92Ala. Distribution of allele 3Gly and 92Ala were significantly higher in the BPAD patients, with odds ratios of 1.489 [95% confidence interval (CI) = 1.124–1.973] and 1.616 [95% CI = 1.275–2.048], respectively. Individuals with two copies of the variant 3Gly or 92Ala were at greater risk of BPAD than individuals with one copy (dose–response manner). Haplotypes ORFa-3Asp-92Ala and ORFa-3Gly-92Ala indicated higher susceptibility for BPAD with odds ratios of 3.759 (95% CI = 2.013–7.020) and 1.292 (95% CI = 1.017–1.642), respectively, while ORFa-3Asp-92Thr probably played a protective role with an odds ratio of 0.395 (95% CI = 0.284–0.549). Conclusion Data generated from this study supported our hypothesis that genetic variations of the DIO2 gene were associated with BPAD and suggested further consideration on the possible involvement of these functionally active variants in the pathophysiology of BPAD.