Reduced mastication is a risk factor for Rome IV postprandial distress syndrome in patients investigated with upper endoscopy.

BACKGROUND AND AIMS: Reduced mastication could force the stomach to do extra work on crushing food and contribute to dyspeptic symptoms. This study aimed to assess the relationship between mastication and dyspepsia. METHODS: This cross-sectional study involved 209 consecutive patients referred for elective upper endoscopy. Before endoscopy, an expert dentist performed an oral examination and scored chewing function in three levels (normal, regular, and reduced), and applied questionnaires for assessment of dyspepsia (Rome IV), xerostomia, and mastication (normal, regular, and reduced). A reduced masticatory function was defined when an oral examination or mastication questionnaire rated the chewing as poor. Associations between mastication, confounders, and dyspepsia were estimated by prevalence ratio [PR (95% Confidence Interval)] using Poisson regression. RESULTS: Thirty-four patients showed relevant organic conditions in the upper gastrointestinal tract (moderate to severe reflux oesophagitis, peptic ulcer, neoplasia, and surgical modification) and were excluded. Among 175 patients with non-organic diseases (aging 51.3 ± 15.7 years; 61.7% women), 50 (28.6%) had reduced mastication, and 125 (71.4%) had normal/regular mastication. After adjusting for age and xerostomia, reduced mastication was associated with postprandial distress syndrome [PR = 1.93 (95%CI 1.27 - 2.91)] but not with epigastric pain syndrome [PR = 1.09 (95%CI 0.75 - 1.60)]. CONCLUSIONS: In patients referred for upper digestive endoscopy, reduced mastication was associated with postprandial distress syndrome but not with epigastric pain syndrome. An interdisciplinary approach with dentists and physicians might benefit dyspeptic patients with postprandial distress syndrome.

Short-term intestinal effects of water intake in fibre supplementation in healthy, low-habitual fibre consumers: a phase 2 clinical trial.

A randomised clinical trial was conducted on 20 healthy, low-habitual fibre consumers to assess the short-term effects of water intake (2 l/day) on fibre supplementation with wheat bran, pectin, and green banana flour. During the 14-days trial, fibre intake doubled in both fibre (n = 10) and fibre/water (n = 10) interventions (p < 0.001), whereas daily water intake increased from 538 to 1990 ml in the fibre/water group (p < 0.001). Weekly bowel movements increased similarly in both interventions (fibre: 6.8-8.8; fibre/water: 8.6-10; p < 0.01), while faecal weight (71-126 g; p = 0.009) increased in the fibre/water group. This group showed higher counts of faecal Bacteroides and Prevotella, Faecalibacterium prausnitzii, and Bifidobacterium, whereas both interventions decreased the count of Desulfovibrio. Transient abdominal symptoms occurred less frequently in the fibre/water than in the fibre group (3 vs. 9 participants; p = 0.020). In healthy, low-habitual fibre consumers, short-term water intake helps the intestinal adaptation to fibre supplementation.CLINICAL TRIAL REGISTRATION NUMBER: NCT02838849.

Reduced masticatory function predicts gastroesophageal reflux disease and esophageal dysphagia in patients referred for upper endoscopy: A cross-sectional study.

BACKGROUND: The role of mastication on gastroesophageal reflux disease (GERD) is unknown. AIMS: To assess whether reduced masticatory function predicts GERD and esophageal dysphagia in patients investigated with upper endoscopy. METHODS: In this cross-sectional study, 179 adult patients referred for elective upper gastrointestinal endoscopy agreed to participate. Before endoscopy, an expert dentist performed an oral examination and scored chewing function in three levels (normal, regular, and reduced). Patients replied questionnaires for assessment of GERD (heartburn, regurgitation, and dysphagia), xerostomia, and mastication (normal, regular, and reduced). Poor chewing was defined when either oral examination or mastication questionnaire rated the chewing function as reduced. Associations of mastication with GERD and dysphagia were estimated using Poisson regression. RESULTS: Eleven patients were excluded. Among 168 analyzed (aging 49.8 ± 15.5 years; 58.9% women), 46 had reduced masticatory function (27.4%), and 122 had regular/normal mastication (72.6%). Reduced mastication was associated with GERD [PR = 1.38 (95%CI 1.12 - 1.70)], adjusting for age, and with esophageal dysphagia [PR = 2.03 (95%CI 1.02 - 4.04)], adjusting for age and xerostomia. CONCLUSIONS: In outpatients referred for upper gastrointestinal endoscopy, reduced masticatory function defined by an expert dentist may be a risk factor for GERD and esophageal dysphagia.

Cancer Cell Fitness Is Dynamic.

Several phenotypes that impact the capacity of cancer cells to survive and proliferate are dynamic. Here we used the number of cells in colonies as an assessment of fitness and devised a novel method called Dynamic Fitness Analysis (DynaFit) to measure the dynamics in fitness over the course of colony formation. DynaFit is based on the variance in growth rate of a population of founder cells compared with the variance in growth rate of colonies with different sizes. DynaFit revealed that cell fitness in cancer cell lines, primary cancer cells, and fibroblasts under unhindered growth conditions is dynamic. Key cellular mechanisms such as ERK signaling and cell-cycle synchronization differed significantly among cells in colonies after 2 to 4 generations and became indistinguishable from randomly sampled cells regarding these features. In the presence of cytotoxic agents, colonies reduced their variance in growth rate when compared with their founder cell, indicating a dynamic nature in the capacity to survive and proliferate in the presence of a drug. This finding was supported by measurable differences in DNA damage and induction of senescence among cells of colonies. The presence of epigenetic modulators during the formation of colonies stabilized their fitness for at least four generations. Collectively, these results support the understanding that cancer cell fitness is dynamic and its modulation is a fundamental aspect to be considered in comprehending cancer cell biology and its response to therapeutic interventions. SIGNIFICANCE: Cancer cell fitness is dynamic over the course of the formation of colonies. This dynamic behavior is mediated by asymmetric mitosis, ERK activity, cell-cycle duration, and DNA repair capacity in the absence or presence of a drug.

Abdominal Palpation Does Not Modify the Number of Bowel Sounds in Healthy Volunteers and Gastrointestinal Outpatients.

BACKGROUND: The effect of abdominal palpation on bowel sounds is controversial. The authors developed an auscultation apparatus to count bowel sounds and determined whether abdominal palpation modifies the number of bowel sounds in healthy volunteers and gastrointestinal outpatients. METHODS: Four medical students developed an auscultation apparatus by attaching a Littmann stethoscope to an electret condenser microphone. The students examined 20 healthy volunteers and 20 gastrointestinal outpatients between March and June 2018. Abdominal auscultation lasting 4 minutes (1-minute each quadrant) was performed before and after abdominal palpation with registration of sound tracings. The software Audacity was used to count the bowel sounds. The effect of palpation on bowel sounds was analyzed using Generalized Estimating Equations. RESULTS: The volunteers were predominantly young (mean ± SD, 21 ± 2 years) and men (70%), whereas the outpatients were older (60 ± 11 years) and women (80%). The apparatus was able to generate sound tracings with good quality from all participants. In the comparison before/after palpation, the number of bowel sounds did not differ either in volunteers (mean ± SD, 12.6 ± 4.7 and 11.6 ± 3.5; P = 0.482) or in patients (15.6 ± 7.5 and 15.8 ± 7.9; P = 0.714). In the analysis of all participants, the difference before-after palpation was not statistically significant (mean ± SD, 14.1 ± 6.3 and 13.7 ± 6.4, respectively; P = 0.550; mean difference = 0.4; 95% CI -1.2 to 2.0) and did not depend on the group studied. CONCLUSIONS: Using an apparatus devised by medical students, the authors found that abdominal palpation did not modify the number of bowel sounds in healthy volunteers and gastrointestinal outpatients.

The somatic mobilization of transposable element mariner-Mos1 during the Drosophila lifespan and its biological consequences.

Transposable elements (TEs) are mobile DNA sequences on genomes. Some elements are able to transpose in somatic cells, a process known as somatic transposition (ST), which has been associated with detrimental biological effects. The mariner-Mos1 element of Drosophila promotes transposition in somatic and germline cells and is an excellent model for studies related to the biological consequence of somatic excision (SE). In this work, we used temperature stress to induce increasing transposition of mariner-Mos1 during different stages of the development of D. simulans, aiming to quantify SE during lifespan. Furthermore, strains of D. melanogaster exhibiting differential expression of mariner-Mos1 were employed for estimating some biological consequences of mariner mobilization. It is shown that SE of mariner-Mos1 was not constant during development; the larval phase had the highest rates while the pupal stage exhibited lower rates, and in the embryonic stage, no difference was detected. SE can be detrimental, as suggested by correlation in SE level and reduction in behavioral activities and embryonic viability. This study showed that mariner-Mos1 SE accumulates during the Drosophila life cycle, and can be involved in detrimental effects.

Acoustic signal of silent tracheal aspiration in children with oropharyngeal dysphagia.

Objetive: The aim of this study was to characterize the acoustic signal of silent tracheal aspiration in children with oropharyngeal dysphagia (OPD). METHOD: Thirty-two children with OPD were examined with combined digital cervical auscultation (DCA) and videofluoroscopic swallow study (VFSS). Power spectral density (PSD, in 1/√Hz) of the acoustic signal from a sequential series of five liquid swallows was used for comparisons between children who silently aspirated and children who did not aspirate on VFSS. Fourteen children were excluded due to either DCA/VFSS artifact or non-silent aspiration (cough, choking). RESULTS: The remaining 18 participants (median age 6 years, range 2-12.8) were classified based on VFSS as aspirators (n = 8) and non-aspirators (n = 10). The PSD curve of aspirators presented an ascending pattern (1st vs. 5th deglutition: 695.2 vs. 4421.9 1/√Hz), while the curve of non-aspirators was flat (1st vs. 5th deglutition: 509 vs. 463.4 1/√Hz), with marked differences being observed from the 3rd measure onwards (p < .001). In this study, DCA was able to identify silent tracheal aspiration in children with OPD. CONCLUSION: This non-invasive technique identified aspiration by an increase in the PSD curve in aspiration sounds.

Cytological and genome size data analyzed in a phylogenetic frame: Evolutionary implications concerning Sisyrinchium taxa (Iridaceae: Iridoideae).

Sisyrinchium is the largest genus of Iridaceae in the Americas and has the greatest amount of cytological data available. This study aimed at investigating how genomes evolved in this genus. Chromosome number, genome size and altitude from species of sect. Viperella were analyzed in a phylogenetic context. Meiotic and pollen analyses were performed to assess reproductive success of natural populations, especially from those polyploid taxa. Character optimizations revealed that the common ancestor of sect. Viperella was probably diploid (2n = 2x =18) with two subsequent polyplodization events. Total DNA content (2C) varied considerably across the phylogeny with larger genomes detected mainly in polyploid species. Altitude also varied across the phylogeny, however no significant relationship was found between DNA content changes and altitude in our data set. All taxa presented regular meiosis and pollen viability (> 87%), except for S. sp. nov. aff. alatum (22.70%), suggesting a recent hybrid origin. Chromosome number is mostly constant within this section and polyploidy is the only source of modification. Although 2C varied considerably among the 20 taxa investigated, the diversity observed cannot be attributed only to polyploidy events because large variations of DNA content were also observed among diploids.

Juice Test for Identification of Nonerosive Reflux Disease in Heartburn Patients.

BACKGROUND/AIMS: Evaluation of esophageal clearance by orange juice swallowing could be useful to identify different categories of gastroesophageal reflux disease. We determined whether a juice test at the beginning of esophageal pH monitoring can identify nonerosive reflux disease (NERD) among heartburn patients. METHODS: Multiple swallows of orange juice (pH 3) were performed at the beginning of esophageal pH monitoring in 71 heartburn patients off acid-suppressive therapy. The area between pH drop below 5 and recovery to 5 was calculated from pH tracings and named Delta5 (mmol∙L⁻¹âˆ™sec). Fifteen healthy subjects served to determine Delta5 cutoff (95th percentile). Patients were classified as NERD, non-NERD (a mix of reflux hypersensitivity, functional heartburn, and undetermined), and erosive disease depending on acid exposure, reflux symptom analysis, and upper endoscopy. RESULTS: Delta5 cutoff in healthy subjects was 251 mmol·L⁻¹âˆ™sec. Among 71 patients, 23 had NERD, 26 had non-NERD, and 22 had erosive disease. Compared to non-NERD, Delta5 was higher in both NERD (median [interquartile range]: 316 [213-472] vs 165 [105-225]; P ＜ 0.01) and erosive disease (310 [169-625] vs 165 [105-225]; P ＜ 0.01). An elevated Delta5 (＞ 251 mmol∙L⁻¹âˆ™sec) showed sensitivity of 74% and specificity of 81% for identification of NERD. Positive and negative likelihood ratios were 3.84 and 0.32 respectively, whereas test accuracy was 78%. CONCLUSIONS: A juice test with calculation of Delta5 helps in the identification of true NERD among heartburn patients with endoscopy-negative reflux disease. In these patients, an elevated Delta5 could make prolonged reflux testing unnecessary.

Cytological and genome size data analyzed in a phylogenetic frame: Evolutionary implications concerning Sisyrinchium taxa (Iridaceae: Iridoideae)

Abstract Sisyrinchium is the largest genus of Iridaceae in the Americas and has the greatest amount of cytological data available. This study aimed at investigating how genomes evolved in this genus. Chromosome number, genome size and altitude from species of sect. Viperella were analyzed in a phylogenetic context. Meiotic and pollen analyses were performed to assess reproductive success of natural populations, especially from those polyploid taxa. Character optimizations revealed that the common ancestor of sect. Viperella was probably diploid (2n = 2x =18) with two subsequent polyplodization events. Total DNA content (2C) varied considerably across the phylogeny with larger genomes detected mainly in polyploid species. Altitude also varied across the phylogeny, however no significant relationship was found between DNA content changes and altitude in our data set. All taxa presented regular meiosis and pollen viability (> 87%), except for S. sp. nov. aff. alatum (22.70%), suggesting a recent hybrid origin. Chromosome number is mostly constant within this section and polyploidy is the only source of modification. Although 2C varied considerably among the 20 taxa investigated, the diversity observed cannot be attributed only to polyploidy events because large variations of DNA content were also observed among diploids.

Influence of genetic, biological and pharmacological factors on levodopa dose in Parkinson's disease.

AIM: Levodopa is first-line treatment of Parkinson's disease motor symptoms but, dose response is highly variable. Therefore, the aim of this study was to determine how much levodopa dose could be explained by biological, pharmacological and genetic factors. PATIENTS & METHODS: A total of 224 Parkinson's disease patients were genotyped for SV2C and SLC6A3 polymorphisms by allelic discrimination assays. Comedication, demographic and clinical data were also assessed. RESULTS: All variables with p < 0.20 were included in a multiple regression analysis for dose prediction. The final model explained 23% of dose variation (F = 11.54; p < 0.000001). CONCLUSION: Although a good prediction model was obtained, it still needs to be tested in an independent sample to be validated.

Gastro-oesophageal reflux disease and dental erosions in adults: influence of acidified food intake and impact on quality of life.

BACKGROUND AND AIM: Gastro-oesophageal reflux disease (GORD) and dental erosions (DE) have an established association. We assessed whether GORD is associated with DE controlling for acidified food intake and their relationships with quality of life (QOL). METHODS: In this cross-sectional study, 419 adult patients who sought dentistry consultation were considered eligible. Patients responded to questionnaires for GORD symptoms, acidified food ingestion and World Health Organization quality of life (WHOQOL Bref), followed by an oral examination, in which DE were characterized according to the Smith & Knight criteria. RESULTS: A total of 417 patients were included (43.8±13.7 years; 68.8% women). There were 143 patients with GORD (34.3%) and 274 controls without GORD. The prevalence of DE was higher in GORD patients compared with the controls (25.9 vs. 17.2%; P=0.041). GORD was associated with DE after adjusting for acidified food intake (P=0.035), with a prevalence ratio of 1.52 (0.95 confidence interval 1.03-2.22). The WHOQOL Bref score was significantly lower in the presence of GORD [median 17.2 (GORD-DE-) vs. 15.4 (GORD+DE+); P<0.01], irrespective of DE. CONCLUSION: In adults examined in a referential dentistry centre in South America, DE were prevalent and significantly associated with GORD. This association was independent of the intake of acidified food in our study. Impairment in QOL was observed in GORD patients irrespective of the presence of DE.

Val66Met BDNF polymorphism is associated with Parkinson's disease cognitive impairment.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases worldwide. Besides characteristic PD motor features, the disease has important non-motor characteristics such as cognitive impairment. The role of genetic factors in cognitive impairment associated with PD is still unclear. In this study, we examined whether BDNF Val66Met was associated with impaired cognition in Parkinson's disease. One hundred and seventy five patients with a clinical diagnosis of Parkinson's disease were included. Global cognitive abilities of the patients were measured by the Mini-Mental State Examination (MMSE). Poisson Regression models were used to test for association between 66Met carriers and cognitive impairment controlling for covariates. Carriers of at least one BDNF 66Met allele presented a higher prevalence of cognitive impairment (p=0.005 RR=1.45 IC=95% [1.1-1.8]). These results suggest a role for BDNF Val66Met polymorphism on cognitive impairment in PD.

The Impact of Gastric Bypass on Gastroesophageal Reflux Disease in Morbidly Obese Patients.

OBJECTIVE: To assess the impact of Roux-en-Y gastric bypass (GBP) on gastroesophageal reflux disease (GERD) in morbidly obese patients. BACKGROUND: Recently, authors have reported that early results of GBP can control GERD. However, longer follow-ups based on objective parameters for GERD are missing. METHODS: Fifty-three patients [15 men (28%), 39 years old (range, 18-59), body mass index = 46 ± 7.7 kg/m2] were consecutively evaluated for GERD irrespectively of related symptoms, before the operation (E1) and at 6 (E2) and 39 ± 7 months postoperatively (E3). The end points were (1) esophageal syndromes based on the Montreal Consensus and (2) an esophageal acid exposure assessment. RESULTS: Body mass index dropped from 46 ± 7.7 kg/m2 at E1 to 30 ± 5.2 kg/m2 at E3. Typical reflux syndrome displayed a significant decrease from 31 (58%) at E1 to 8 (15%) at E2 and 5 (9%) at E3. Statistically significant differences occurred between E1 and both postoperative evaluations (P < 0.001). Reflux esophagitis was detected in 24 (45%), 17 (32%), and 10 patients (19%) at E1, E2, and E3, respectively (P = 0.002). The incidence of GERD decreased in 34 (64%) and 21 (40%) patients at E1 and E2, respectively, and then in 12 (23%) patients at E3. DeMeester scores reduced from 28.6 (E1) to 9.4 (E2) and 1.2 (E3) (P < 0.001). CONCLUSIONS: For most morbidly obese patients, in addition to causing significant weight loss, GBP reduces GERD symptoms, improves reflux esophagitis, and decreases esophageal acid exposure for longer than 3 years.

High interpopulation homogeneity in Central Argentina as assessed by Ancestry Informative Markers (AIMs).

The population of Argentina has already been studied with regard to several genetic markers, but much more data are needed for the appropriate definition of its genetic profile. This study aimed at investigating the admixture patterns and genetic structure in Central Argentina, using biparental markers and comparing the results with those previously obtained by us with mitochondrial DNA (mtDNA) in the same samples. A total of 521 healthy unrelated individuals living in 13 villages of the Córdoba and San Luis provinces were tested. The individuals were genotyped for ten autosomal ancestry informative markers (AIMs). Allele frequencies were compared with those of African, European and Native American populations, chosen to represent parental contributions. The AIM estimates indicated a greater influence of the Native American ancestry as compared to previous studies in the same or other Argentinean regions, but smaller than that observed with the mtDNA tests. These differences can be explained, respectively, by different genetic contributions between rural and urban areas, and asymmetric gene flow occurred in the past. But a most unexpected finding was the marked interpopulation genetic homogeneity found in villages located in diverse geographic environments across a wide territory, suggesting considerable gene flow.

Corticosteroid receptor genes and childhood neglect influence susceptibility to crack/cocaine addiction and response to detoxification treatment.

The aim of this study was to analyze hypotheses-driven gene-environment and gene-gene interactions in smoked (crack) cocaine addiction by evaluating childhood neglect and polymorphisms in mineralocorticoid and glucocorticoid receptor genes (NR3C2 and NR3C1, respectively). One hundred thirty-nine crack/cocaine-addicted women who completed 3 weeks of follow-up during early abstinence composed our sample. Childhood adversities were assessed using the Childhood Trauma Questionnaire (CTQ), and withdrawal symptoms were assessed using the Cocaine Selective Severity Assessment (CSSA) scale. Conditional logistic regression with counterfactuals and generalized estimating equation modeling were used to test gene-environment and gene-gene interactions. We found an interaction between the rs5522-Val allele and childhood physical neglect, which altered the risk of crack/cocaine addiction (Odds ratio = 4.0, P = 0.001). Moreover, a NR3C2-NR3C1 interaction (P = 0.002) was found modulating the severity of crack/cocaine withdrawal symptoms. In the post hoc analysis, concomitant carriers of the NR3C2 rs5522-Val and NR3C1 rs6198-G alleles showed lower overall severity scores when compared to other genotype groups (P-values ≤ 0.035). This gene-environment interaction is consistent with epidemiological and human experimental findings demonstrating a strong relationship between early life stress and the hypothalamic-pituitary-adrenal (HPA) axis dysregulation in cocaine addiction. Additionally, this study extended in crack/cocaine addiction the findings previously reported for tobacco smoking involving an interaction between NR3C2 and NR3C1 genes.

Is there a role for ADORA2A polymorphisms in levodopa-induced dyskinesia in Parkinson's disease patients?

AIM: Levodopa is first line treatment of Parkinson's disease (PD). However, its use is associated with the presence of motor fluctuations and dyskinesias. In recent years, adenosine A2A receptor (A2AR) is rising as a therapeutic target for PD. The aim of the present study was to investigate whether ADORA2A is associated with levodopa adverse effects. PATIENTS & METHODS: Two hundred and eight PD patients on levodopa therapy were investigated. rs2298383 and rs3761422 at the ADORA2A gene were genotyped by allelic discrimination assays. RESULTS: A trend for association was observed for both polymorphism and diplotypes with dyskinesia. CONCLUSION: The present results should be considered as positive preliminary evidence. Further studies are needed to determine the association between ADORA2A and dyskinesia. Original submitted 3 December 2014; Revision submitted 13 February 2015.

The lactase persistence genotype is a protective factor for the metabolic syndrome.

The Metabolic Syndrome (MetS) is defined as a pattern of metabolic disturbances, which include central obesity, insulin resistance and hyperglycemia, dyslipidemia, and hypertension. Milk has been promoted as a healthy beverage that can improve the management of MetS. Most human adults, however, down-regulate the production of intestinal lactase after weaning. Lactase encoded by the LCT gene is necessary for lactose digestion. The -13910C > T SNP (rs4988235) is responsible for the lactase persistence phenotype in European populations. We herein investigated whether the lactase persistence genotype is also associated with the MetS in subjects from a Brazilian population of European descent. This study consisted of 334 individuals (average age of 41 years) genotyped by PCR-based methods for the -13910C > T SNP. Clinical data were assessed and the genotypes were tested for their independent contribution to the MetS using chi-square tests and multiple logistic regression analysis. Univariate analyses showed that hypertension and MetS prevalence were higher in individuals with the lactase non-persistence genotype than in lactase persistence subjects. Furthermore, lactase persistence was associated with a lower risk for MetS (OR = 0.467; 95% CI 0.264-0.824; p = 0.009). These results suggest that LCT genotypes can be a valuable tool for the management of MetS treatment.

MR and GR functional SNPs may modulate tobacco smoking susceptibility.

A number of studies have demonstrated that stress is involved in all aspects of smoking behavior, including initiation, maintenance and relapse. The mineralocorticoid (MR) and glucocorticoid (GR) receptors are expressed in several brain areas and play a key role in negative feedback of the hypothalamic-pituitary-adrenal (HPA) axis. As nicotine increases the activation of the HPA axis, we wondered if functional SNPs (single nucleotide polymorphisms) in MR and GR coding genes (NR3C2 rs5522 and NR3C1 rs6198, respectively) may be involved in smoking susceptibility. The sample included 627 volunteers, of which 514 were never-smokers and 113 lifetime smokers. We report an interaction effect between rs5522 and rs6198 SNPs. The odds ratio (OR) for the presence of the NR3C2 rs5522 Val allele in NR3C1 rs6198 G carriers was 0.18 (P = 0.007), while in rs6198 G noncarriers the OR was 1.83 (P = 0.027). We also found main effects of the NR3C1 rs6198 G allele on number of cigarettes smoked per day (P = 0.027) and in total score of the Fagerström Test for Nicotine Dependence (P = 0.007). These findings are consistent with a possible link between NR3C2 and NR3C1 polymorphisms and smoking behavior and provide a first partial replication for a nominally significant GWAS finding between NR3C2 and tobacco smoking.