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Determination of NAT2 Activity in the US Population by Use of Caffeine Metabolite Ratios in Spot Urine Samples: NHANES 2009–2010
Author(s) -
Pao ChingI,
Sternberg Maya R.,
Rybak Michael,
Pfeiffer Christine M.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.908.6
Subject(s) - caffeine , metabolite , urine , population , chemistry , endocrinology , metabolism , medicine , physiology , arylamine n acetyltransferase , n acetyltransferase , pharmacokinetics , acetylation , biochemistry , environmental health , gene
N ‐acetyltransferase‐2 (NAT2) is a phase II enzyme which is involved in the metabolism of many xenobiotics. The genetic polymorphisms of NAT2 gene, yielding either slow or faster acetylation phenotypes, usually influence individual variations in response to medication and detoxification. A slow NAT2activity has been associated with increased cancer risk. NAT2 is involved in the formation of 5‐acetyl‐amino‐6‐formylamino‐3‐methyluracil (AFMU) from a series of intermediates of caffeine metabolism. A metabolic ratio (MR) of urine AFMU and other caffeine metabolites, resulting from either a test dose or regular dietary intake of caffeine, can be used to assess NAT2 activity. In this study we described NAT2 activity in the US population ≥6 y by selected demographic, lifestyle and physiologic variables. We used spot urine concentrations of 5‐acetylamino‐6‐amino‐3‐methyluracil (AAMU; the stable breakdown product of AFMU), 1‐methylxanthine (1X), and 1‐methyluric acid (1U)from the cross‐sectional NHANES 2009–2010 to calculate NAT2 activity by use of the MR [AAMU/(AAMU+1X+1U)]. We excluded individuals taking prescription medications known to interfere with caffeine metabolism and individuals with evidence of insufficient caffeine exposure to reliably calculate the NAT2 MR (n = 2197). We used Spearman correlation to examine the relation of NAT2 MR with continuous variables, and performed bivariate comparisons of unadjusted geometric mean (GM) NAT2 MR for categorical variables. We observed a weak correlation of NAT2 MR with age (Spearman ρ = 0.14, P <0.0001). NAT2 activity was highest in Hispanics and lowest in non‐Hispanic blacks (Wald F, P = 0.005). No statistically significant differences in NAT2activity were observed among sexes. NAT2 activity was higher in individuals who fasted >8 h vs. ≤8 h (Wald F, P =0.0056). No trend in GM NAT2 MR was observed with alcohol consumption (limited to individuals ≥20 y) and no significant difference was observed among smokers vs. non‐smokers as categorized by serum cotinine concentration. NAT2 activity was significantly higher in individuals with evidence of impaired liver function (i.e. AST or ALT>70 U/L vs. ≤70 U/L) (Wald F P =0.0096), but no difference was observed among diabetes status (yes vs. no basedon a physician's diagnosis) or inflammation status (serum CRP ≥5 mg/L vs. <5mg/L). The GM of MR was significantly higher in the urine samples collected in the morning vs. in the evening (Wald F, P trend = 0.013). Our observations withNAT2 activity and race‐ethnicity appeared to be consistent with what is known regarding race‐associated polymorphisms. We believe our study is the first report of using urine caffeine MRs in spot urine samples to estimate NAT2 activity in a representative sample of the US population.