Relationships of PROP Taste Phenotype, Taste Receptor Genotype, and Oral Nicotine Replacement Use

Abstract

Introduction: Recommended dosage of oral nicotine replacement therapy (NRT) product is often not achieved in smoking cessation attempts. n-6-propylthiouracil (PROP) bitter taste phenotype may be a potential risk factor for non-adherence to oral NRT products due to their bitter taste. There is limited literature on this phenotype in the context of smoking and none in relation to oral NRT pharmacotherapy. Methods: The association of PROP taste phenotype with NRT usage and sensory response to products was examined. In a cross-over experimental design, 120 participants received a 1 week supply of nicotine inhalers and 1 week of nicotine lozenges with random assignment to order. Mixed effects linear model analyses were conducted. Results: PROP taste phenotype and taste receptor genotype were not associated with NRT usage or sensory response to NRT, after adjusting for other factors. However, PROP non-tasters used a higher number of lozenges per day (continuous exposure) than nicotine cartridges (intermittent exposure). Unexpectedly, half of baseline PROP non-tasters shifted to taster phenotype 2 weeks after smoking cessation or reduction. Menthol cigarette smokers identified higher NRT strength of sensation scores than nonmenthol smokers. Taste receptor genotype was related to PROP taste phenotype (Kendall τ = .591, p = .0001). Conclusions: A nonsignificant relationship of PROP phenotype and NRT usage may be associated with NRT under-dosing and limited variance in the outcome variable. PROP non-tasters' greater use of lozenges is consistent with nicotine exposure being less aversive to non-tasters. Further research of this and other factors impacting NRT usage are warranted to effectively inform smoking cessation pharmacotherapy.

Dose-Dependent Effects of L-Arginine on PROP Bitterness Intensity and Latency and Characteristics of the Chemical Interaction between PROP and L-Arginine

“…In conclusion, it is becoming increasingly clear that PROP tasting is a complex phenotype influenced by a variety of factors including the functional interaction between TAS2R38 and the gustin gene that controls the taste bud trophic factor known as gustin protein [ 28 ], differences in messenger RNA expression in fungiform papillae [ 84 ], as well as environmental factors such as age and smoking [ 85 , 86 ]. Our recent work adds an additional dimension to our understanding of these phenotypic differences by focusing on the permissive role of the salivary Ps-1 protein and its constituent amino acid L-Arg in PROP taste responsiveness [ 35 , 36 ].…”

Factors Influencing the Phenotypic Characterization of the Oral Marker, PROP

“…Very little work has been done on the acute effects of smoking abstinence, although one study showed partial recovery of taste acuity following 12 h of smoking abstinence [ 132 ]. To our knowledge, the study by Ahijevych et al [ 57 ] is the only clinical trial to examine relationships between PROP tasting and smoking cessation in individuals with access to nicotine replacement therapy (NRT). Results showed that PROP non-tasters were more likely to use nicotine lozenges, which is consistent with the notion that oral nicotine exposure is less aversive to non-taster individuals.…”

“…The shaded box identifies a small group of participants who were classified as PROP non-tasters at both. Data are from Ahijevych et al [ 57 ] with permission.…”

“…This conclusion may be based, in part, on data showing that at high NaCl concentrations (>0.35 M), NaCl ratings are not independent of PROP taster status and diverge in super tasters [ 41 ]. Nevertheless, the use of NaCl as a reference standard has been successfully employed by numerous laboratories across the globe [ 17 , 18 , 27 , 33 , 34 , 38 , 39 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. Data described later in this review illustrate this point.…”

“…The 1-solution and paper disk methods rely on empirically-derived cutoff scores for PROP taster classification. These techniques have been used in numerous investigations in our work [ 17 , 18 , 27 , 33 , 38 , 39 , 43 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ] and the work of others [ 58 , 59 , 60 , 61 ]. PROP classifications obtained with this suite of methods is highly correlated with all known TAS2R38 genotypes [ 27 , 33 , 64 , 65 , 66 , 67 ] and differences in physiological responses such as prefrontal cortex activity [ 68 ] and degree of activation of peripheral taste function [ 69 , 70 ].…”