Poetsch M, Czerwinski M, Wingenfeld L, Vennemann M, Bajanowski T.
Institute of Legal Medicine, University Hospital Essen, Hufelandstr. 55, 45122, Essen, Germany
http://www.ncbi.nlm.nih.gov/pubmed/20198379
Smoking during pregnancy has been identified as one of the major modifiable risk factors of sudden infant death syndrome (SIDS). It has been demonstrated that the risk of SIDS increases with increasing cigarette consumption. A variety of hypotheses have been proposed for explanation, including a genetic predisposition. The flavin-monooxygenase 3 (FMO3) is one of the enzymes metabolising nicotine, and several polymorphisms have already been described in this gene. Here, we studied variations in the exons and introns of the FMO3 gene by direct sequencing analysis and minisequencing in 159 SIDS cases and 170 controls. The three common variants G472A (E158K), G769A (V257M) and A923G (E308G) in the exons of the FMO3 gene were identified. The homozygote 472AA genotype occurred more frequently in SIDS cases than in controls (p = 0.0054) and was more frequent in those SIDS cases for which the mothers reported heavy smoking (p = 0.0084). This study is the first to demonstrate a gene-environment interaction in SIDS. The findings suggest that the common polymorphism G472A of FMO3 could act as an additional genetic SIDS risk factor in children whose mothers smoke. Parents who could pass on the 472A allele should be informed of the increased risk associated with smoking. Smoking mothers should be strongly advised to give up smoking during pregnancy and for at least the first year of the child's life.As previously mentioned in this blog, FMO3 enzyme deals with 1,000's of substrates, probably mostly oxidizing them for detoxification. Considering the amount of substrates it deals with, it is surprising that the pharmaceutical industry probably neglect the enzyme when testing new drugs for bad reactions. As well as many drugs, FMO3 will deal with many other sulfides, amines and phosphorous containing compounds. Dr Cashman has mentioned previously that FMO3 plays a minor but very important role in detoxifying nicotine.
These German researchers have been involved at looking at the possible cuases of Sudden Infant Death (SID) Syndrome. Apparently one hypothesis was that pregnant women who smoke heavily may be genetically predisposed to SID, with the FMO3 enzyme being investigated for a possible genetic connection in this study.
They checked the mothers of SID cases for common polymorphs (variants) of the FMO3 enzyme. They found that there was a higher rate of those homozygote (i.e. 2 copies) of the 472AA polymorph, especially among some of the heaviest smokers, and regard it as statistically significant. They also say it is the first study to show a genetic-environmental relation to SID.
Hopefully this will interest other researchers around the world to investigate FMO3, which seems to be the 'neglected' xenobiotic enzyme, despite possibly being the busiest of them. Any research into FMO3 is likely to be beneficial to TMAU sufferers, and possibly other systemic odor sufferers, given the range of sulfides and amines it deals with.
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