RGD Reference Report - Genetic variation in catechol-O-methyltransferase (COMT) and obesity in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial. - Rat Genome Database

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Genetic variation in catechol-O-methyltransferase (COMT) and obesity in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial.

Authors: Wang, SS  Morton, LM  Bergen, AW  Lan, EZ  Chatterjee, N  Kvale, P  Hayes, RB  Chanock, SJ  Caporaso, NE 
Citation: Wang SS, etal., Hum Genet. 2007 Aug;122(1):41-9. Epub 2007 May 12.
RGD ID: 2289713
Pubmed: PMID:17497175   (View Abstract at PubMed)
DOI: DOI:10.1007/s00439-007-0374-7   (Journal Full-text)

Catechol-O-methyltransferase (COMT) is an important modulator in the catabolism of extraneural dopamine, which plays an important role in drug reward mechanisms. It is hypothesized that genetic variations in the COMT gene, which can result in a three to fourfold difference in COMT enzyme activity, may be associated with several reward-motivated behaviors. The aim of our study was to examine the relationship between COMT polymorphisms with smoking, obesity and alcohol. Three single nucleotide polymorphisms (SNPs) in COMT were genotyped in 2,371 participants selected randomly from the screening arm of the PLCO Cancer Screening Trial after stratifying by sex, age, and smoking status. Smoking, obesity, and alcohol consumption were assessed by questionnaire. SNP and haplotype associations were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from conditional logistic regression models, adjusted for race/ethnicity. The COMT Ex4-76C > G (Leu136Leu) polymorphism was statistically significantly associated with individuals who had >30% increases in BMI from ages 20 to 50 years, compared to those with 0-5% increase in BMI (0-5%) over the same age period: (CC is referent; OR(CG )= 1.42, OR(GG )= 1.46, P (trend )= 0.06). By sex, the increased risk was further pronounced among females (OR(CG )= 1.50, OR(GG )= 2.10, P (trend )= 0.03). Consistent with our analyses of single polymorphisms, individuals whose BMI increased >30% from ages 20 to 50 years were more likely than individuals with 0-5% increases in BMI to possess COMT haplotypes [COMT Ex3-104C > T-COMT Ex4-76 C > G-COMT Ex4-12 A > G] that included the variant allele for COMT Ex4-76 C > G: C-G-G (T-C-A is referent: OR(C-G-G )= 1.33, 95% CI 1.01-1.77) and C-G-A (OR(C-G-A )= 1.79, 95% CI 0.72-4.49). We observed no association between any of the COMT polymorphisms with smoking behavior or alcohol intake. The COMT Ex4-76C > G (Leu136Leu) polymorphism appears to play a role in large increases in BMI. The null association with smoking and alcohol and the pronounced association with increasing BMI among women further implicates COMT's role in estrogen metabolism as a potentially culpable pathway. Our results support a need for comprehensive evaluation of COMT variations and their functional relevance as COMT may be an important molecular target to evaluate for new treatments regarding obesity.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
COMTHumanobesity susceptibilityIAGP DNA:polymorphism:exonRGD 
ComtRatobesity susceptibilityISOCOMT (Homo sapiens)DNA:polymorphism:exonRGD 
ComtMouseobesity susceptibilityISOCOMT (Homo sapiens)DNA:polymorphism:exonRGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
COMTHumanIncreased body mass index  IAGP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Comt  (catechol-O-methyltransferase)

Genes (Mus musculus)
Comt  (catechol-O-methyltransferase)

Genes (Homo sapiens)
COMT  (catechol-O-methyltransferase)


Additional Information