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Thursday, March 15, 2012

New FMO3 paper on pubmed : polymorphisms in a Turkish group

paper : common FMO3 variants
A new paper has appeared on Pubmed about the enzyme FMO3. There is no new information on FMO3, only a study of the incidence of 3 common FMO3 'variants' in a Turkish group. It is good to see a toxicology department taking an interest in FMO3, as it is a drug metabolizing enzyme and predicting reactions to drugs will likely be what leads to most FMO3 research in the future.

In the study they look to see how common the 3 missense variants at codons 158, 257, and 308 are among a group of Turks. FMO3 is made up of a 532 amino acid sequence (532 codons). A missense variant is where an incorrect amino acid is inserted. Normally this would make no difference in itself, however in combination with other missense codons it can result in loss of function to some degree.
FMO3 has 532 codons

Common variants at codons 158, 257, and 308

E158K missense variant

amino acid should be E but K is inserted

E & K are amino acid symbols

E is glutamic Acid
K is lysine
For instance, the faults at codons 158 and 308 on the same allelle (i.e. from the same parent) is known to possibly cause slight loss of function. It is estimated that perhaps 50% of caucasians carry the 158 missense variant and perhaps 20% carry the 308 variant.

In the Turkish group in the study, it was found that 80% either were totally 'normal' at the codons 158,257,308 (ie 'EVE') or carried the 158 variant (KVE) but all would be predicted as having normal FMO3 function. That, therefore, leaves 20% with various combinations of the 3 variants. The various combinations do not mean they will definitely have some loss of function, but in some combinations, it can, and it makes it more likely.

Flavin-containing monooxygenase 3 gene polymorphisms in turkish population

References :
FMO3 letter to editor 2000
TMAU article on NIH.gov website

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