The Val/Met functional polymorphism in COMT confers susceptibility to bipolar disorder: evidence from an association study and a meta-analysis
- 248 Downloads
The COMT gene is considered as one of the prominent candidate genes for susceptibility to BP, and most studies focused a functional polymorphism in the gene: the Val/Met polymorphism (rs4680). However, results from these studies are sometimes contradictory, due to small sample size or heterogeneity. In this study, we first investigate the possible association between the Val/Met polymorphism in COMT and bipolar disorder in the Han population, which has never been done before. Then a systematic meta-analysis was conducted to determine if the low-activity allele (Met) increases the risk of BP in different ethnic groups. A total of 478 BP patients and 469 healthy subjects were recruited in our case/control study. MIX software package was employed to perform the meta-analysis on 19 studies after careful search and selection. We observed statistically-significant differences in allele (p = 0.00060) and genotype (p = 0.00203) frequencies between patients and controls in our samples. The meta-analysis also provided a significant pooled OR for association of the Met allele in rs4680 with BP in the total population (p = 0.0223) and in the Asian population (p = 0.0232). Although a significant pooled OR was also found for the Caucasian population (p = 0.0409) after one of the studies as discussed below was removed, the role for Val/Met polymorphism in BP in Caucasian ethnicity was not yet to be confirmed. In conclusion, the low-activity allele (Met) of rs4680 in COMT gene possibly confers risk for bipolar disorder in the Han population, while it needs further evidence for concluding its association with BP in the Caucasian population.
KeywordsAssociation Bipolar disorder COMT Meta-analysis
Bipolar I disorder
Bipolar II disorder
Genome-wide association studies
Minor allele frequency
Open reading frames
This work was supported by grants (KSCX2-YW-R-01, 05JC14090, 2006AA02A407, 2006CB910601, 2006BAI05A05, 07DZ22917), Chinese Nutrition Society (05015), Shanghai-Unilever Research and Development Fund (06SU07007) and the National Natural Science Foundation of China, Shanghai Leading Academic Discipline Project (B205).
- Dickerson FB, Boronow JJ, Stallings C et al (2006) The catechol O-methyltransferase Val158Met polymorphism and herpes simplex virus type 1 infection are risk factors for cognitive impairment in bipolar disorder: additive gene-environmental effects in a complex human psychiatric disorder. Bipolar Disord 8:124–132PubMedCrossRefGoogle Scholar
- Domschke K, Deckert J, O’Donovan MC et al (2007) Meta-analysis of COMT val158met in panic disorder: ethnic heterogeneity and gender specificity. Am J Med Genet B Neuropsychiatr Genet 144:667–673Google Scholar
- Halleland H, Lundervold AJ, Halmoy A et al (2008) Association between catechol O-methyltransferase (COMT) haplotypes and severity of hyperactivity symptoms in adults. Am J Med Genet B Neuropsychiatr Genet 150B(3):403–410Google Scholar
- Meyer-Lindenberg A, Nichols T, Callicott JH et al (2006) Impact of complex genetic variation in COMT on human brain function. Mol Psychiatry 11:867–877, 797Google Scholar