GeneSet Information

Tier II GS135535 • caffeine metabolism QTL 2 (Cafq2, Published QTL Chr 4)


QTL associated with caffeine metabolism QTL 2. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (111547663)


QTL-Cafq2-Mouse-Chr 4









Casley WL, Menzies JA, Whitehouse LW, Moon TW


Detection of quantitative trait loci affecting caffeine metabolism by interval mapping in a genome-wide scan of C3H/HeJ x APN F(2) mice.


Drug metabolism and disposition: the biological fate of chemicals Dec 1999, Vol 27, pp. 1375-80


Caffeine metabolite ratios have been widely used to measure cytochrome P-450 1A2 activity in humans. Serum paraxanthine/caffeine ratio is one such index of this activity. We had previously demonstrated genetic variation of this trait among inbred mouse strains. In the present study, we have undertaken a genome-wide scan for quantitative trait loci affecting this trait with an interval mapping approach on an F(2) intercross population of acetaminophen nonsusceptible and C3H/HeJ inbred mice. A statistically significant association (log-likelihood ratio = 25.0) between a locus on chromosome 9, which colocalized with the murine Cyp1a2 locus, and the plasma paraxanthine/caffeine ratio was identified. This result suggested the presence of an expression polymorphism affecting this gene. A second locus was identified on chromosome 1 (log-likelihood ratio = 9.7) for which no obvious candidate gene has been identified. The influence of this locus on the paraxanthine/caffeine index was more significant among males (log-likelihood ratio = 6.3) than females (log-likelihood ratio = 3.6). A third locus was identified on chromosome 4 with a less statistically robust association (log-likelihood ratio = 3.4) to the paraxanthine/caffeine phenotype. Collectively, these three loci accounted for 63.2% of the variation observed in the F(2) population for this phenotype. These results demonstrate the potential for genetic variation arising from factors other than CYP1A2 activity to influence the plasma paraxanthine/caffeine ratio in mice. This study demonstrates the utility of quantitative genetics in the analysis of polygenic drug metabolism. PUBMED: 10570017
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Annotation Information

Genetic Variation (D014644)
Chromosomes, Human, Pair 9 (D002899)
Chromosomes, Human, Pair 4 (D002894)
Cytochrome P-450 CYP1A2 (D019388)
Genetics (D005823)
Chromosomes (D002875)
Chromosomes, Human, Pair 1 (D002878)
Acetaminophen (D000082)
Quantitative Trait Loci (D040641)
Cytochrome P-450 Enzyme System (D003577)
Caffeine (D002110)
Polymorphism, Genetic (D011110)
Mice, Inbred Strains (D008815)
Cytochromes (D003580)
Association (D001244)
Metabolism (D008660)
metabolic process (GO:0008152)
drug metabolic process (GO:0017144)
chromosome (GO:0005694)

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