Cotinine is the test used to check whether somebody smokes. It turns out how fast you clear it is partly genetic — which matters because smokers of different ancestries get lung cancer at different rates even after adjusting for how much they smoke.
When nicotine enters the body it is broken down, mostly into cotinine, and cotinine is then cleared. Cotinine lasts far longer than nicotine, which is why it is the standard measure of tobacco exposure: it is what a laboratory tests to check whether someone smokes, whether they have quit, and how much second-hand smoke they are getting.
That makes it a measuring instrument. And a measuring instrument that varies between people for reasons unrelated to what it is measuring is worth understanding.
This research did not begin as a curiosity about metabolism. It began with an unexplained fact: smokers' lung cancer risk differs by race and ethnicity even after adjusting for how much they smoke.
One candidate explanation is dose. Two people who smoke the same number of cigarettes do not necessarily absorb, metabolise and clear the same amount of nicotine — and if the amount that stays in the body differs, so does the exposure that matters.
The study genotyped 2,239 smokers from the Multiethnic Cohort and measured nicotine and its metabolites in urine. The composition of that sample is why it can answer the question at all:
Almost every study on this site is overwhelmingly European-ancestry, and we say so on almost every page. This one was built the other way round, because the difference between groups was the question. It is worth pointing at as a design rather than passing over.
Of 11,892,802 variants analysed, 1,241 were strongly associated with cotinine glucuronidation, and 490 of those were also associated with nicotine glucuronidation. The gene doing most of the work is UGT2B10 — a UDP-glucuronosyltransferase, one of the enzymes that attaches a sugar to a compound to make it water-soluble enough to be excreted.
Two of the positions on this page, rs141360540 and rs115219551, are in UGT2B10 itself.
Cotinine is used to decide things. Insurers use it to price policies. Transplant programmes and some surgical services use it to verify abstinence. Studies use it to classify people as smokers or non-smokers.
All of that assumes the number means the same thing in everybody. If clearance is partly genetic, then two people with identical smoking behaviour can produce different numbers, and the direction of that difference is not random with respect to ancestry.
This does not make the test useless — it remains far better than asking people. It does mean a cotinine level is a measurement with a person-specific scale factor in it, and that is not usually how it is treated.
Nothing you should act on. There is no clinical test for nicotine clearance, no guideline uses one, and nothing here changes how to stop smoking.
What does change outcomes is well known and has nothing to do with genotype: stopping, with help. See smoking cessation medicines for where a genotype does briefly enter that conversation, and smoking behaviour and nicotine dependence for the genetics of the habit itself rather than of the metabolite.
Source. Patel et al. (Cancer Epidemiol Biomarkers Prev 2015) conducted a genome-wide association study of nicotine and cotinine glucuronidation in 2,239 smokers from the Multiethnic Cohort Study — 437 European Americans, 364 African Americans, 453 Latinos, 674 Japanese Americans and 311 Native Hawaiians — with urinary concentrations of nicotine and its metabolites determined. Among 11,892,802 variants analysed, 1,241 were strongly associated with cotinine glucuronidation, of which 490 were also associated with nicotine glucuronidation. The authors conclude that genetic variation in UGT2B10 contributes significantly to nicotine and cotinine glucuronidation. The stated motivation is that the lung cancer risk of smokers varies by race and ethnicity even after adjustment for smoking, and that differences in nicotine dose and metabolism may be relevant to that disparity.
Positions listed here. Eight recorded by the collector from this study, including rs141360540 and rs115219551 in UGT2B10. Several of the others carry non-gene locus identifiers from the original annotation and are presented as positions rather than as genes.
Interpretation of the biomarker. Cotinine and its glucuronide are widely used to verify smoking status and to quantify exposure. Genetic variation in glucuronidation capacity introduces between-person variation in the ratio of parent compound to conjugate that is independent of exposure, and the allele frequencies involved differ between the populations in which the biomarker is applied. This is a measurement-validity consideration rather than a treatment one.
Clinical use. None. No guideline directs nicotine replacement, varenicline or bupropion by glucuronidation genotype, and there is no clinical assay for it. Smoking cessation is managed with behavioural support and pharmacotherapy chosen on the clinical picture.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Nicotine and Cotinine Metabolism comes down to these specific, well-studied positions — not a diagnosis.
It means the number carries a person-specific scale factor that is partly genetic, so identical smoking can produce different readings. The test is still far better than asking. But it is used to price insurance, verify abstinence before surgery and classify people in research, and all of those assume the number means the same thing in everybody.
Because the difference between groups was the question. Smokers of different ancestries develop lung cancer at different rates even after adjusting for how much they smoke, and nicotine dose and metabolism are candidate explanations. A single-ancestry study could not have asked it.
No. There is no clinical assay for this and no guideline uses one. What works for stopping is well established and has nothing to do with your genotype: support plus medication, chosen on your circumstances.
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