Journal of Neural Transmission

, Volume 116, Issue 10, pp 1193–1200 | Cite as

The Val/Met functional polymorphism in COMT confers susceptibility to bipolar disorder: evidence from an association study and a meta-analysis

  • Zhao Zhang
  • Klaus Lindpaintner
  • Ronglin Che
  • Zangdong He
  • Peng Wang
  • Ping Yang
  • Guoyin Feng
  • Lin He
  • Yongyong Shi
Basic Neurosciences, Genetics and Immunology - Original Article


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.


Association Bipolar disorder COMT Meta-analysis 



Bipolar disorder


Bipolar I disorder


Bipolar II disorder




Genome-wide association studies


Hardy–Weinberg equilibrium


Linkage disequilibrium


Minor allele frequency


Membrane-bound COMT


Open reading frames


Odds ratio


Soluble COMT


Transmission-disequilibrium testing


Velo-cardio-facial syndrome



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).

Supplementary material

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Zhao Zhang
    • 1
    • 2
    • 3
    • 8
  • Klaus Lindpaintner
    • 4
  • Ronglin Che
    • 1
    • 2
    • 3
  • Zangdong He
    • 1
    • 2
    • 3
  • Peng Wang
    • 5
  • Ping Yang
    • 5
  • Guoyin Feng
    • 6
  • Lin He
    • 1
    • 2
    • 3
    • 7
    • 8
  • Yongyong Shi
    • 1
    • 2
    • 3
    • 7
    • 8
  1. 1.Bio-X CenterShanghai Jiao Tong UniversityShanghaiPeople’s Republic of China
  2. 2.Changning Mental Health CenterThe Bio-X Center HospitalShanghaiPeople’s Republic of China
  3. 3.Institute for Nutritional Sciences, Shanghai Institutes of Biological SciencesChinese Academy of SciencesShanghaiChina
  4. 4.Roche (China) LtdShanghaiPeople’s Republic of China
  5. 5.Wuhu No. 4 People’s HospitalWuhuPeople’s Republic of China
  6. 6.Shanghai Institute of Mental HealthShanghaiChina
  7. 7.Institute of Biomedical SciencesFudan UniversityShanghaiPeople’s Republic of China
  8. 8.Key Laboratory of Developmental Genetics and Neuropsychiatric DiseasesMinistry of Education, Shanghai Jiao Tong UniversityShanghaiPeople’s Republic of China

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