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Association of CHRN genes with "dizziness" to tobacco.

ABSTRACT: The neuronal nicotinic receptor genes (CHRN) have been implicated in a variety of smoking-related behaviors. Here we tested for association between an early subjective response phenotype, "dizziness," and 226 single nucleotide polymorphisms (SNPs) in CHRN genes. The sample included 789 nicotine-dependent cases and 811 controls, where early "dizziness" reports were significantly associated with case/control status (P < 0.0001). Multiple SNPs in the putative promoter region of the CHRNB3 gene were nominally associated with "dizziness" experience from the first few cigarettes (P < 0.01). Cell culture studies were conducted to examine the ability of different haplotypes in the CHRNB3 promoter to drive luciferase expression. Data from these experiments support the hypothesis that different alleles in the CHRNB3 upstream promoter region may lead to different levels of RNA expression. In addition, a novel finding of association between SNPs in the CHRNA10 gene reached experiment-wide empirical significance (P = 0.048), which implicates another CHRN gene as being involved in early subjective response to tobacco.

SUBMITTER: Ehringer MA

PROVIDER: S-EPMC2878135 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Association of CHRN genes with "dizziness" to tobacco.

Ehringer Marissa A MA McQueen Matthew B MB Hoft Nicole R NR Saccone Nancy L NL Stitzel Jerry A JA Wang Jen C JC Bierut Laura J LJ

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20100301 2

The neuronal nicotinic receptor genes (CHRN) have been implicated in a variety of smoking-related behaviors. Here we tested for association between an early subjective response phenotype, "dizziness," and 226 single nucleotide polymorphisms (SNPs) in CHRN genes. The sample included 789 nicotine-dependent cases and 811 controls, where early "dizziness" reports were significantly associated with case/control status (P < 0.0001). Multiple SNPs in the putative promoter region of the CHRNB3 gene were ...[more]

PMID: 19760673

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Project description:Importance:Catastrophizing is a maladaptive thought process that involves irrational fear and worry about anticipated or actual symptoms. Although clinically relevant, the role of catastrophizing in patients with chronic dizziness or imbalance has not yet been explored to our knowledge. Objectives:To validate a measure of dizziness catastrophizing and to assess its association with dizziness-related disability compared with other negative affect constructs (eg, anxiety and depression). Design, Setting, and Participants:For this retrospective medical record review, the Dizziness Catastrophizing Scale (DCS), a dizziness-specific catastrophizing assessment tool, was adapted from the previously validated Pain Catastrophizing Scale. Psychometric evaluation of the DCS was performed. In addition, the associations of dizziness catastrophizing and positive and negative affectivity with dizziness-related disability were assessed using structural equation modeling and regression analyses. Data were collected using a retrospective medical record review from April 27, 2010, to June 25, 2014. The dates of analysis were June 3 to August 15, 2017. The setting was the Multidisciplinary Neurotology Clinic at the Toronto General Hospital (Toronto, Ontario, Canada). Participants were 457 adult outpatients with dizziness or imbalance who were referred to the clinic. Main Outcomes and Measures:Psychometric properties of the DCS and its association with dizziness-related disability, as measured with the Dizziness Handicap Inventory. Results:Among 457 patients (mean [SD] age, 53.4 [15.4] years; 154 [33.7%] male), the DCS demonstrated good convergent (r = 0.78, P < .001) and discriminant validity (r = -0.40, P < .001) with the negative and positive affectivity, respectively; internal consistency (α = .95); and test-retest reliability (intraclass correlation coefficient, 0.92; P < .001 at the 95% CI). An exploratory dimension reduction analysis revealed a single latent component of the DCS. The results of the structural equation modeling and regression analyses revealed that dizziness catastrophizing, although associated with negative affectivity (eg, symptoms of anxiety and depression), was independently associated with dizziness-related disability (standardized β = 0.378; P < .001). Furthermore, a strong association was found between catastrophizing and dizziness-related disability across different dizziness-related diagnoses (r ≥ 0.6; P < .001). Conclusions and Relevance:In this study, the DCS was a valid and reliable measure for evaluating catastrophic thinking in patients with dizziness, which was independently associated with dizziness-related disability. Future studies should investigate the influence of alleviating symptoms of catastrophizing on functional outcomes in patients with dizziness or imbalance, the results of which will help guide novel approaches to the clinical care of patients with chronic dizziness.

Project description:BackgroundAssociations between dizziness-related handicap and a variety of self-reported measures have been reported. However, research regarding associations between dizziness-related handicap and aspects of functioning that includes both physical tests and self-reported measures is scarce.ObjectiveThe purpose of the study was to describe the variations in signs and symptoms in people with persistent dizziness using physical tests and self-reported outcomes across three severity levels of the Dizziness Handicap Inventory (DHI) and investigate their associations with the DHI.MethodParticipants with persistent dizziness (n = 107) were included in this cross-sectional study. The participants underwent (1) physical tests (gait tests, grip strength, body flexibility, and movement-induced dizziness) and completed questionnaires regarding (2) psychological measures (Mobility Inventory of Agoraphobia, Body Sensation Questionnaire, Agoraphobic Cognitions Questionnaire, and Hospital Depression and Anxiety Questionnaire), and (3) fatigue, dizziness severity, and quality of life (Chalders Fatigue Scale, Vertigo Symptom Scale-Short Form, and EQ visual analog scale), in addition to the DHI. Data were presented by descriptive statistics for three DHI severity levels (mild, moderate, and severe). A multiple linear backward regression analysis was conducted for each group of measures in relation to the DHI total score, with additional analyses adjusting for age and sex. Based on these results, significant associations were tested in a final regression model.ResultsWith increasing severity levels of DHI, the participants demonstrated worse performance on most of the physical tests (preferred and fast gait velocity, dizziness intensity after head movements), presented with worse scores on the self-reported measures (avoidance behavior, fear of bodily sensation, fear of fear itself, psychological distress, fatigue, dizziness severity, quality of life). After adjusting for age and sex, significant associations were found between total DHI and avoidance behavior, psychological distress, dizziness severity, and quality of life, but not with any of the physical tests, explaining almost 56% of the variance of the DHI total score.ConclusionThere was a trend toward worse scores on physical tests and self-reported measurements with increasing DHI severity level. The DHI seems to be a valuable tool in relation to several self-reported outcomes; however, several signs and symptoms may not be detected by the DHI, and thus, a combination of outcomes should be utilized when examining patients with persistent dizziness.

Project description:BackgroundThe impact of long-term dizziness is considerable both on the personal level and in society and may lead to self-imposed restrictions in daily activities and social relations due to fear of triggering the symptoms. Musculoskeletal complaints seem to be common in persons with dizziness, but studies addressing these complaints as a widespread occurrence, are scarce. This study aimed to examine the occurrence of widespread pain in patients with long-term dizziness and investigate the associations between pain and dizziness symptoms. Further, to explore whether diagnostic belonging is related to the occurrence of pain.MethodsThis cross-sectional study was conducted in an otorhinolaryngology clinic and included 150 patients with persistent dizziness. The patients were categorized into three groups: episodic vestibular syndromes, chronic vestibular syndromes, and non-vestibular group. The patients completed questionnaires on dizziness symptoms, catastrophic thinking, and musculoskeletal pain when entering the study. Descriptive statistics were used to describe the population, and associations between pain and dizziness were investigated by linear regression.ResultsPain was reported by 94.5% of the patients. A significantly higher prevalence of pain was reported in all the ten pain sites examined compared to the general population. Number of pain sites and pain intensity were associated with the dizziness severity. Number of pain sites was also associated with dizziness-related handicap, but not with catastrophic thinking. There was no association between pain intensity and dizziness-related handicap or catastrophic thinking. Pain was equally distributed in the diagnostic groups.ConclusionPatients with long-term dizziness have a considerably higher prevalence of pain and number of pain sites than the general population. Pain co-exists with dizziness and is associated with dizziness severity. These findings may indicate that pain should be systematically assessed and treated in patients with persisting dizziness.

Dataset Information

Association of CHRN genes with "dizziness" to tobacco.

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Association of CHRN genes with "dizziness" to tobacco.

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