Predictors of apical periodontitis in root canal treated teeth from an adult Nepalese subpopulation: a cross-sectional study.

BACKGROUND: Endodontic literature search revealed that no study has been conducted to evaluate the prevalence of apical periodontitis (AP) in root canal treated teeth from an adult Nepalese population of Madhesh Province. Consequently, little is known about the extent and risk factors associated with it. This study aimed to determine AP prevalence in root canal treated teeth from an adult Nepalese subpopulation and to analyze the related risk factors including age, sex, tooth type, type of coronal restoration and quality of root canal treatment and coronal restoration as predictors of AP. METHODS: Digital panoramic radiographs were evaluated. Periapical status of 300 root canal-treated teeth was scored by using the periapical index. The quality of root canal treatment and coronal restorations were categorized as adequate or inadequate through radiographic and clinical evaluation. The data were analyzed using univariate and multivariate logistic regression models. RESULTS: Prevalence of AP in the present study was 31.7%. In 45.7% of the treated teeth, quality of root canal treatment was adequate whereas 46% of the cases had adequate coronal restorations. Multivariate logistic regression analysis revealed statistically significant associations and remarkably increased risk for AP in teeth with inadequate root canal treatment (odds ratio [OR] = 7.92; 95% CI: 3.96-15.82; p < 0.001) whereas lower risk for AP was found in females (OR = 0.51; 95% CI: 0.28-0.90; p = 0.021) and in teeth restored with crown (OR = 0.22; 95% CI: 0.09-0.51; p < 0.001) and filling (OR = 0.18; 95% CI: 0.08-0.42; p < 0.001). Quality of coronal restoration, tooth type and age of the patient were not found to be the predictors of AP. CONCLUSIONS: Within the limits of this study, a high prevalence of AP and poor overall quality of root canal treatment and coronal restoration was found in the subpopulation studied. Quality of root canal treatment, type of coronal restoration and sex of the patient are significant predictors of possible AP development in root canal treated teeth. Substantial efforts are needed to improve the endodontic treatment standards.

Does BRAF mutation status and related clinicopathological factors affect the recurrence rate of ameloblastoma? A systematic review, meta-analysis and metaregression.

OBJECTIVES: This review aims to analyse the recurrence rate in BRAFv600e+ and BRAFv600e- ameloblastomas and explore its association with clinicopathological variables. METHODS: A comprehensive search was conducted using databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, Google Scholar and grey literature, without any limitation on start date or language up to 20 June 2023. A random effect meta-analysis was conducted and Metaregression analyses were performed based on available clinicopathological factors. RESULTS: Fifteen studies met the criteria for meta-analysis of outcomes. There was no significant difference in overall recurrence rates between the two groups (risk difference = 0.001, p-value = 0.987). Increasing male:female ratio in the BRAFv600e+ group was associated with a lower reported recurrence, suggesting a higher recurrence rate in females. The odds of having mandibular lesion were four times higher in BRAFv600e+ cases compared to BRAFv600e- cases (confidence interval: 2.121-7.870, p < 0.001, I2 = 28.37%). CONCLUSION: Within the BRAFv600e+ group, females showed a higher reported recurrence rate. This specific clinical group may benefit from BRAFv600e mutation investigation and potential upscaled surgical treatment and additional BRAF inhibitor therapy, which needs validation in future studies.

Relationship Between Psychosocial Stress and Blood Pressure: The National Heart, Lung, and Blood Institute Family Heart Study.

Introduction: Various domains of psychosocial stress have been significantly related to blood pressure. However, ambiguity is present in how these relationships are defined in the literature. Objective: To add to the existing literature and examine the relationship between psychosocial stress (financial strain and job strain) and other cofactors on blood pressure. Methods: This secondary analysis is designed to analyze the relationship between levels of job and financial stress and blood pressure outcomes among participants in the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study 2004-2008. The descriptive, cross-sectional design uses data from a subset of study participants, 350 White and 195 Black (n = 545), 338 female (62%), and all aged 18-56 years. Psychosocial stress was measured using the Singh Stress Scale. Resting systolic (SBP) and diastolic (DBP) blood pressure values obtained on a stress reactivity protocol day in the primary study, as well as calculated mean arterial pressure (MAP) were used for this analysis. Multivariate linear regression analyses were used to explore the relationship between psychosocial stress and blood pressure. Results: In this young cohort, self-report of either financial strain or job strain was associated with lower blood pressure levels than those of participants who reported neither stressor. Differential sex and race effects appear to contribute to these results. Blood pressure levels were not significantly associated with self-report of both stressors. Conclusion: Understanding the effects of various forms of stress on blood pressure may inform more precise HTN risk-factor screening and interventions to improve BP management.

Effectiveness of dexamethasone or adrenaline with lignocaine 2% for prolonging inferior alveolar nerve block: a randomized controlled trial.

OBJECTIVES: Inferior alveolar nerve block (IANB) is commonly used for mandibular dentoalveolar surgery. The objective of this study was to evaluate and compare the effectiveness of coadministration of dexamethasone (4 mg/mL) or adrenaline (0.01 mg/mL) as an adjuvant with lignocaine 2% in IANB during third molar surgery (TMS). PATIENTS AND METHODS: This double-blind, randomized controlled trial was conducted between March and August 2020. The investigators screened patients needing elective TMS under local anesthesia. Based on strict inclusion and exclusion criteria, patients were enrolled in this study. These patients were assigned randomly into two study groups: dexamethasone group (DXN) or adrenaline group (ADN). Outcome variables were postoperative edema, trismus, visual analogue scale (VAS), perioperative analgesia, onset time, and duration of IANB. RESULTS: Eighty-three patients were enrolled in this study, of whom 23 (27.7%) were eliminated or excluded during follow-up. This study thus included data from 60 samples. Mean age was 32.28±11.74 years, including 28 females (46.7%) in the ADN (16 patients, 57.1%) and DXN (12 patients, 42.9%) groups. The duration of action for DXN (mean±standard deviation [SD], 4:02:07±0:34:01 hours; standard error [SE], 0:06:00 hours; log-rank P=0.001) and for ADN (mean±SD, 1:58:34±0:24:52 hours; SE, 0:04:42 hours; log-rank P=0.001) were found. Similarly, time at which 1st analgesic consume and total number of nonsteroidal antiinflammatory drugs need to rescue postoperative analgesia was found statistically significant between study groups (t (58)=-11.95; confidence interval, -2:25:41 to -1:43:53; P=0.001). Early-hours VAS was also significantly different between the study groups. CONCLUSION: A single injection of dexamethasone prolongs the duration of action of lignocaine 2% IANB. Additionally, it can be used in cases where adrenaline is contraindicated.

Pain perception and dental anxiety during periodontal probing in patients visiting community oral health programme: a cross sectional study.

BACKGROUND: Periodontal probing is one of the basic clinical oral examination procedures. It is carried out to assess the severity of gingival and periodontal disease. The experience of pain during probing may discourage patients. So, this study was conducted to estimate the pain perception and dental anxiety experienced during periodontal probing in patients visiting the community oral health programmes of B. P. Koirala Institute of Health Sciences (BPKIHS). METHODS: A cross-sectional study was conducted among 100 participants of community oral health programmes of BPKIHS. Demographic profile, WHO modified Community Periodontal Index (CPI) 2013, Pain perception via Visual Analogue Scale (VAS Scores) and Short Version of Spielberger State-Trait Anxiety Inventory (STAI) Self-evaluation Questionnaire (Y-6 item) were assessed. Mean ± SD and Spearman correlation for pain and anxiety were computed. RESULTS: Only 10% of the study participants had healthy gingiva and 12% had periodontal pockets. Pain perception and dental anxiety was present in the participants. The participants experienced very little pain (6.75 ± 10.65) during periodontal probing. The overall anxiety score was 13.37 ± 1.81. There was a very weak correlation between the VAS Scores and the anxiety scores of the participants. CONCLUSION: This study concludes that pain perception and anxiety are low during periodontal probing. There was no correlation between bleeding on probing with pain and anxiety among the people visiting community oral health programmes of BPKIHS.

Knowledge of novel coronavirus disease (COVID-19) among dental surgeons of Nepal: a nationwide study.

BACKGROUND: COVID-19 is an emerging respiratory disease caused by a novel coronavirus. There is not much evidence assessing the knowledge of dental surgeons regarding COVID-19. This study was conducted to assess the knowledge of COVID-19 among dental surgeons of Nepal. METHODS: A web-based cross-sectional study was conducted among registered dental surgeons of Nepal. Ethical approval was obtained. Consent was taken, and knowledge on COVID-19 was assessed via a pre-tested structured questionnaire using Google form. The form was emailed to the participants. Descriptive analysis was performed using frequency, percentage, median and inter-quartile range. Man-Whitney test and Kruskal-Wallis tests were carried out to see the difference in knowledge score. P-value < 0.05 was considered statistically significant. RESULTS: Total 227 dental surgeons responded to the questionnaire (male: 46.4%; female: 53.7%). Almost two-third ( 65.2% ) of the respondents were B.D.S. (Bachelor of Dental Surgery) graduates. Only 29.1% worked in the government hospitals. 17.6% were currently involved in COVID-19 management. Of the participants, 87.7% knew about the condition of the requirement of Personal Protective Equipment (PPE) but only 29.1% could correctly answer the framed question for PPE. The median knowledge score calculated was 14.0 (8.0-18.0). The bivariate analysis showed a statistically significant difference in knowledge score among the age group ≥30 years and < 30 years (p = 0.013); M.D.S. (Master of Dental Surgery) graduate and B.D.S. graduate (0.041); dental surgeons of government healthcare facilities and other healthcare facilities (p <  0.001); dental surgeons of COVID-19 centers and non-COVID-19 centers (0.002). CONCLUSION: The dental surgeons of Nepal have a good knowledge of COVID-19, and they can be utilized for assisting in the management of COVID-19 cases in Nepal.

Evaluating the precision of EBF1 SNP x stress interaction association: sex, race, and age differences in a big harmonized data set of 28,026 participants.

In prior work, we identified a novel gene-by-stress association of EBF1's common variation (SNP rs4704963) with obesity (i.e., hip, waist) in Whites, which was further strengthened through multiple replications using our synthetic stress measure. We now extend this prior work in a precision medicine framework to find the risk group using harmonized data from 28,026 participants by evaluating the following: (a) EBF1 SNPxSTRESS interaction in Blacks; (b) 3-way interaction of EBF1 SNPxSTRESS with sex, race, and age; and (c) a race and sex-specific path linking EBF1 and stress to obesity to fasting glucose to the development of cardiometabolic disease risk. Our findings provided additional confirmation that genetic variation in EBF1 may contribute to stress-induced human obesity, including in Blacks (P = 0.022) that mainly resulted from race-specific stress due to "racism/discrimination" (P = 0.036) and "not meeting basic needs" (P = 0.053). The EBF1 gene-by-stress interaction differed significantly (P = 1.01e-03) depending on the sex of participants in Whites. Race and age also showed tentative associations (Ps = 0.103, 0.093, respectively) with this interaction. There was a significant and substantially larger path linking EBF1 and stress to obesity to fasting glucose to type 2 diabetes for the EBF1 minor allele group (coefficient = 0.28, P = 0.009, 95% CI = 0.07-0.49) compared with the same path for the EBF1 major allele homozygotes in White females and also a similar pattern of the path in Black females. Underscoring the race-specific key life-stress indicators (e.g., racism/discrimination) and also the utility of our synthetic stress, we identified the potential risk group of EBF1 and stress-induced human obesity and cardiometabolic disease.

Systolic Blood Pressure and Socioeconomic Status in a large multi-study population.

The present study used harmonized data from eight studies (N = 28,891) to examine the association between socioeconomic status (SES) and resting systolic blood pressure (SBP). The study replicates and extends our prior work on this topic by examining potential moderation of this association by race and gender. We also examined the extent to which body mass index (BMI), waist circumference (WC), and smoking might explain the association between SES and SBP. Data were available from six race/gender groups: 9200 Black women; 2337 Black men; 7248 White women; 6519 White men; 2950 Hispanic women; and 637 Hispanic men. Multivariable regression models showed that greater annual household income was associated with lower SBP in all groups except Hispanic men. The magnitude and form of this negative association differed across groups, with White women showing the strongest linear negative association. Among Black men and Hispanic women, the association was curvilinear: relatively flat among lower income levels, but then negative among higher income ranges. Education also was independently, negatively related to SBP, though evidence was weaker for race and gender differences in the strength of the association. Higher BMI and WC were associated with higher SBP, and current smoking with lower SBP. Inclusion of these risk factors resulted in only a modest change in the magnitude of the SBP and SES relation, accounting on average about 0.4 mmHg of the effect of income and 0.2 mmHg of the effect of education-effects unlikely to be clinically significant. Further understanding of mechanisms underlying the association between SBP and SES may improve risk stratification in clinical settings and potentially inform interventions aimed at reductions in social disparities in health.

Fluoride Level in Drinking Water Sources of Eastern Nepal.

BACKGROUND: Water is essential for the survival of every living organism of this planet, we humans being no exception to this fact. In context of oral health promotion, fluoride when consumed in recommended level decreases the solubility of enamel to acidic exposure and improves the strength of dental enamel that eventually helps reduce dental caries.So, this study was conducted to estimate the fluoride concentration in drinking water of eastern development region Nepal. METHODS: Water samples (165) were randomly collected from drinking water sources of Eastern Development Region, Nepal. Three categories of water samples (municipal, natural, packaged bottle water) each from three most populated cities of every district in the region were collected. The water samples were collected in autoclaved polypropylene plastic vessels. American Public Health Association 4500 F- D method was used for fluoride estimation. RESULTS: Majority of the water samples (88.2%) had fluoride concentration below the optimum as per WHO guideline. Median fluoride concentration of municipal water supply, natural water resources and packaged bottle water was 0.09 ppm (<0.05 to 1.11 ppm), 0.13 ppm (<0.05 to 1.80 ppm) and 0.05ppm (<0.05 ppm to 0.78 ppm) respectively. Median fluoride concentration of Himalayan region, hill region and terai region was 0.17 ppm, 0.10 ppm and 0.07 ppm respectively. Overall median fluoride concentration of eastern development region Nepal was 0.08 ppm (<0.05 pmm to 1.80 ppm). CONCLUSIONS: This study illustrated that fluoride concentration of most of the drinking water resources of eastern Nepal was below the recommended optimum level as per WHO guidelines.

Lack of Association of a Functional Polymorphism in the Serotonin Receptor Gene With Body Mass Index and Depressive Symptoms in a Large Meta-Analysis of Population Based Studies.

The serotonin receptor 5-HTR2C is thought to be involved in the function of multiple brain structures. Consequently, the HTR2C gene has been studied extensively with respect to its association with a variety of phenotypes. One coding variant in the HTR2C gene, Cys23Ser (rs6318), has been associated with depressive symptoms. and adiposity; however, these findings have been inconsistent. The reasons for this mixed picture may be due to low statistical power or due to other factors such as failure to account for possible interacting environmental factors, such as psychosocial stress. Further, the literature around this polymorphism is marked by limited inclusion of persons of African ancestry. The present study sought to overcome these limitations and definitively determine the relationship of this polymorphism with depressive and obesity phenotypes in a large sample meta-analysis. Thus, we harmonized individual level data from 10 studies including the Women's Health Initiative, CARDIA, ARIC, Framingham Offspring, and the Jackson Heart Study, resulting in a sample of 27,161 individuals (10,457 Black women, 2,819 Black men, 7,419 White women, and 6,466 White men). We conducted a random effects meta-analysis using individual level data to examine whether the Cys23Ser variant-either directly, or conditionally depending on the level of psychosocial stress-was associated with depressive symptoms and body mass index (BMI). We found that psychosocial stress was associated with both depression and BMI, but that Cys23Ser was not directly associated with, nor did it modify the associations of psychosocial stress with depression or BMI. Thus, in the largest study of this polymorphism, we have determined that rs6318 is not associated with depression, or BMI.

Developing a synthetic psychosocial stress measure and harmonizing CVD-risk data: a way forward to GxE meta- and mega-analyses.

OBJECTIVES: Among many challenges in cardiovascular disease (CVD) risk prediction are interactions of genes with stress, race, and/or sex and developing robust estimates of these interactions. Improved power with larger sample size contributed by the accumulation of epidemiological data could be helpful, but integration of these datasets is difficult due the absence of standardized phenotypic measures. In this paper, we describe the details of our undertaking to harmonize a dozen datasets and provide a detailed account of a number of decisions made in the process. RESULTS: We harmonized candidate genetic variants and CVD-risk variables related to demography, adiposity, hypertension, lipodystrophy, hypertriglyceridemia, hyperglycemia, depressive symptom, and chronic psychosocial stress from a dozen studies. Using our synthetic stress algorithm, we constructed a synthetic chronic psychosocial stress measure in nine out of twelve studies where a formal self-rated stress measure was not available. The mega-analytic partial correlation between the stress measure and depressive symptoms while controlling for the effect of study variable in the combined dataset was significant (Rho = 0.27, p < 0.0001). This evidence of the validity and the detailed account of our data harmonization approaches demonstrated that it is possible to overcome the inconsistencies in the collection and measurement of human health risk variables.

Amelogenesis Imperfecta: A Case Series from the Community.

Amelogenesis Imperfecta is a hereditary disorder affecting the formation of enamel structure. Two female children and one male (11 years, 12 years and 6 years respectively) reported with chief complaint of yellowish discoloration of teeth since their childhood. They reported that they had similar discoloration in their deciduous teeth. Clinical examination showed generalized deposits of plaque and calculus, yellowish discoloration of the teeth with chipping off of the incisal and cuspal enamel structures. OPG revealed thin lining of enamel with thick dentin layer and pulp chamber. PA view revealed unfused anterior fontanels and lateral cephalogram indicated vertebrae in growing phase. The patients were instructed to maintain proper oral hygiene and regular follow up till the growth cessation. Permanent skeletal, functional, esthetic needs is addressed after growth completion. Oral rehabilitation through multidisciplinary approach can certainly provide a good prognosis and patients were counselled and motivated to maintain good oral hygiene. Keywords: Amelogenesis Imperfecta; esthetic; yellowish discoloration.

Brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism is associated with disease severity and incidence of cardiovascular events in a patient cohort.

BACKGROUND: The rs6265 (Val66Met) single-nucleotide polymorphism in the BDNF gene has been related to a number of endophenotypes that have in turn been shown to confer risk for atherosclerotic cardiovascular disease (CVD). To date, however, very few studies have examined the association of the Val66Met single-nucleotide polymorphism with CVD clinical outcomes. METHODS: In a cohort of 5,510 Caucasian patients enrolled in the CATHeterization GENetics (CATHGEN) study at Duke University Hospital between 2001 and 2011, we determined the severity of coronary artery disease (CAD) and CVD event incidence through up to 11.8years of follow-up. We examined the association of Val66Met genotype with time-to-death or myocardial infarction, adjusting for age, sex, CAD risk variables, and CAD severity measures. RESULTS: The Val/Val genotype was associated with a higher risk than Met carriers for clinical CVD events (P=.034, hazard ratio 1.12, 95% CI 1.01-1.24). In addition, compared with Met carriers, individuals with the Val/Val genotype had a greater odds of having more diseased vessels (odds ratio 1.17, 95% CI 1.06-1.30, P=.002), and lower left ventricular ejection fraction (ß=-0.72, 95% CI, -1.42 to -0.02, P=.044). CONCLUSIONS: The Val/Val genotype was associated with greater severity of CAD and incidence of CVD-related clinical events in a patient sample. If these findings are confirmed in further research, intervention studies in clinical groups with the Val/Val genotype could be undertaken to prevent disease and improve prognosis.

Case-Only Survival Analysis Reveals Unique Effects of Genotype, Sex, and Coronary Disease Severity on Survivorship.

Survival bias may unduly impact genetic association with complex diseases; gene-specific survival effects may further complicate such investigations. Coronary artery disease (CAD) is a complex phenotype for which little is understood about gene-specific survival effects; yet, such information can offer insight into refining genetic associations, improving replications, and can provide candidate genes for both mortality risk and improved survivorship in CAD. Building on our previous work, the purpose of this current study was to: evaluate LSAMP SNP-specific hazards for all-cause mortality post-catheterization in a larger cohort of our CAD cases; and, perform additional replication in an independent dataset. We examined two LSAMP SNPs-rs1462845 and rs6788787-using CAD case-only Cox proportional hazards regression for additive genetic effects, censored on time-to-all-cause mortality or last follow-up among Caucasian subjects from the Catheterization Genetics Study (CATHGEN; n = 2,224) and the Intermountain Heart Collaborative Study (IMHC; n = 3,008). Only after controlling for age, sex, body mass index, histories of smoking, type 2 diabetes, hyperlipidemia and hypertension (HR = 1.11, 95%CI = 1.01-1.22, p = 0.032), rs1462845 conferred significantly increased hazards of all-cause mortality among CAD cases. Even after controlling for multiple covariates, but in only the primary cohort, rs6788787 conferred significantly improved survival (HR = 0.80, 95% CI = 0.69-0.92, p = 0.002). Post-hoc analyses further stratifying by sex and disease severity revealed replicated effects for rs1462845: even after adjusting for aforementioned covariates and coronary interventional procedures, males with severe burden of CAD had significantly amplified hazards of death with the minor variant of rs1462845 in both cohorts (HR = 1.29, 95% CI = 1.08-1.55, p = 0.00456; replication HR = 1.25, 95% CI = 1.05-1.49, p = 0.013). Kaplan-Meier curves revealed unique cohort-specific genotype effects on survival. Additional analyses demonstrated that the homozygous risk genotype ('A/A') fully explained the increased hazard in both cohorts. None of the post-hoc analyses in control subjects were significant for any model. This suggests that genetic effects of rs1462845 on survival are unique to CAD presence. This represents formal, replicated evidence of genetic contribution of rs1462845 to increased risk for all-cause mortality; the contribution is unique to CAD case status and specific to males with severe burden of CAD.

Computing a Synthetic Chronic Psychosocial Stress Measurement in Multiple Datasets and its Application in the Replication of G × E Interactions of the EBF1 Gene.

Chronic psychosocial stress adversely affects health and is associated with the development of disease [Williams, 2008]. Systematic epidemiological and genetic studies are needed to uncover genetic variants that interact with stress to modify metabolic responses across the life cycle that are the proximal contributors to the development of cardiovascular disease and precipitation of acute clinical events. Among the central challenges in the field are to perform and replicate gene-by-environment (G × E) studies. The challenge of measurement of individual experience of psychosocial stress is magnified in this context. Although many research datasets exist that contain genotyping and disease-related data, measures of psychosocial stress are often either absent or vary substantially across studies. In this paper, we provide an algorithm to create a synthetic measure of chronic psychosocial stress across multiple datasets, applying a consistent criterion that uses proxy indicators of stress components. We validated the computed scores of chronic psychosocial stress by observing moderately strong and significant correlations with the self-rated chronic psychosocial stress in the Multi-Ethnic Study of Atherosclerosis Cohort (Rho = 0.23, P < 0.0001) and with the measures of depressive symptoms in five datasets (Rho = 0.15-0.42, Ps = 0.005 to <0.0001) and by comparing the distributions of the self-rated and computed measures. Finally, we demonstrate the utility of this computed chronic psychosocial stress variable by providing three additional replications of our previous finding of gene-by-stress interaction with central obesity traits [Singh et al., 2015].

Gene by stress genome-wide interaction analysis and path analysis identify EBF1 as a cardiovascular and metabolic risk gene.

We performed gene-environment interaction genome-wide association analysis (G × E GWAS) to identify SNPs whose effects on metabolic traits are modified by chronic psychosocial stress in the Multi-Ethnic Study of Atherosclerosis (MESA). In Whites, the G × E GWAS for hip circumference identified five SNPs within the Early B-cell Factor 1 (EBF1) gene, all of which were in strong linkage disequilibrium. The gene-by-stress interaction (SNP × STRESS) term P-values were genome-wide significant (Ps = 7.14E-09 to 2.33E-08, uncorrected; Ps = 1.99E-07 to 5.18E-07, corrected for genomic control). The SNP-only (without interaction) model P-values (Ps = 0.011-0.022) were not significant at the conventional genome-wide significance level. Further analysis of related phenotypes identified gene-by-stress interaction effects for waist circumference, body mass index (BMI), fasting glucose, type II diabetes status, and common carotid intimal-medial thickness (CCIMT), supporting a proposed model of gene-by-stress interaction that connects cardiovascular disease (CVD) risk factor endophenotypes such as central obesity and increased blood glucose or diabetes to CVD itself. Structural equation path analysis suggested that the path from chronic psychosocial stress to CCIMT via hip circumference and fasting glucose was larger (estimate = 0.26, P = 0.033, 95% CI = 0.02-0.49) in the EBF1 rs4704963 CT/CC genotypes group than the same path in the TT group (estimate = 0.004, P = 0.34, 95% CI = -0.004-0.012). We replicated the association of the EBF1 SNPs and hip circumference in the Framingham Offspring Cohort (gene-by-stress term P-values = 0.007-0.012) as well as identified similar path relationships. This observed and replicated interaction between psychosocial stress and variation in the EBF1 gene may provide a biological hypothesis for the complex relationship between psychosocial stress, central obesity, diabetes, and cardiovascular disease.

A putatively functional polymorphism in the HTR2C gene is associated with depressive symptoms in white females reporting significant life stress.

Psychosocial stress is well known to be positively associated with subsequent depressive symptoms. Cortisol response to stress may be one of a number of biological mechanisms that links psychological stress to depressive symptoms, although the precise causal pathway remains unclear. Activity of the x-linked serotonin 5-HTR2C receptor has also been shown to be associated with depression and with clinical response to antidepressant medications. We recently demonstrated that variation in a single nucleotide polymorphism on the HTR2C gene, rs6318 (Ser23Cys), is associated with different cortisol release and short-term changes in affect in response to a series of stress tasks in the laboratory. Based on this observation, we decided to examine whether rs6318 might moderate the association between psychosocial stress and subsequent depressive symptoms. In the present study we use cross-sectional data from a large population-based sample of young adult White men (N = 2,366) and White women (N = 2,712) in the United States to test this moderation hypothesis. Specifically, we hypothesized that the association between self-reported stressful life events and depressive symptoms would be stronger among homozygous Ser23 C females and hemizygous Ser23 C males than among Cys23 G carriers. In separate within-sex analyses a genotype-by-life stress interaction was observed for women (p = .022) but not for men (p = .471). Homozygous Ser23 C women who reported high levels of life stress had depressive symptom scores that were about 0.3 standard deviations higher than female Cys23 G carriers with similarly high stress levels. In contrast, no appreciable difference in depressive symptoms was observed between genotypes at lower levels of stress. Our findings support prior work that suggests a functional SNP on the HTR2C gene may confer an increased risk for depressive symptoms in White women with a history of significant life stress.

Socioeconomic indices as independent correlates of C-reactive protein in the National Longitudinal Study of Adolescent Health.

OBJECTIVES: To examine the association between socioeconomic status (SES) and C-reactive protein (CRP) to understand how SES may increase the risk of cardiovascular disease and thus identify targets for prevention measures. METHODS: Path models were used to examine direct and indirect associations of four indices of SES (objective early life built environment ratings, parental and participant education, and income) with CRP measured during early adulthood using data from the National Longitudinal Adolescent Health Study (n = 11,371; mean age = 29 years, range = 24-32 years; 53.8% women, 28.0% black participants). The present study examined potential mediation of the association of SES with CRP by way of body mass index (BMI), smoking, and alcohol consumption within white and black men and women. RESULTS: BMI was a mediator of the relation between parent education and CRP for white men (path coefficient [γ] = -0.05, p < .001) and women (γ = -0.05, p < .001). Smoking mediated the income-CRP (γ = -0.01, p < .01) and the education-CRP (γ = -0.07, p < .001) relation for white men. BMI mediated the relation between all measures of SES and CRP for white women (γ values between -0.02 and -0.05; p values < .01). None of the risk factors mediated the SES-CRP relation in black participants. CONCLUSIONS: These findings indicate that the association of SES with CRP is influenced by both the timing and type of SES measure examined. In addition, race and sex play a role in how potential mediators are involved with the SES-CRP relationship, such that BMI and smoking were mediators in white men, whereas BMI was the sole mediator in white women.

Chronic family stress moderates the association between a TOMM40 variant and triglyceride levels in two independent Caucasian samples.

TOMM40 SNP rs157580 has been associated with triglyceride levels in genome-wide association studies (GWAS). Chronic caregiving stress moderates the association between triglyceride levels and a nearby SNP rs439401 that is associated with triglyceride levels in GWAS. Here, we report data from two independent Caucasian samples (242 U.S. women and men; 466 Danish men) testing the hypothesis that chronic family stress also moderates the association between rs157580 and triglyceride levels. The interaction of rs157580 and family stress in predicting triglyceride levels was statistically significant in the U.S. sample (p=0.004) and marginally significant (p=0.075) in the Danish sample. The G allele of rs157580 was associated with increased triglyceride levels among family stressed cases in both samples compared with A/A cases, but not among controls. Chronic family stress moderates the association of rs157580 variants with triglyceride levels and should be taken into account for disease risk assessment and potential intervention.

A functional polymorphism in the 5HTR2C gene associated with stress responses also predicts incident cardiovascular events.

Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (rs6318) of the 5HTR2C gene located on the X-chromosome is associated with hypothalamic-pituitary-adrenal axis response to a stress recall task, and with endophenotypes associated with cardiovascular disease (CVD). These findings suggest that individuals carrying the rs6318 Ser23 C allele will be at higher risk for CVD compared to Cys23 G allele carriers. The present study examined allelic variation in rs6318 as a predictor of coronary artery disease (CAD) severity and a composite endpoint of all-cause mortality or myocardial infarction (MI) among Caucasian participants consecutively recruited through the cardiac catheterization laboratory at Duke University Hospital (Durham, NC) as part of the CATHGEN biorepository. Study population consisted of 6,126 Caucasian participants (4,036 [65.9%] males and 2,090 [34.1%] females). A total of 1,769 events occurred (1,544 deaths and 225 MIs; median follow-up time = 5.3 years, interquartile range = 3.3-8.2). Unadjusted Cox time-to-event regression models showed, compared to Cys23 G carriers, males hemizygous for Ser23 C and females homozygous for Ser23C were at increased risk for the composite endpoint of all-cause death or MI: Hazard Ratio (HR) = 1.47, 95% confidence interval (CI) = 1.17, 1.84, p = .0008. Adjusting for age, rs6318 genotype was not related to body mass index, diabetes, hypertension, dyslipidemia, smoking history, number of diseased coronary arteries, or left ventricular ejection fraction in either males or females. After adjustment for these covariates the estimate for the two Ser23 C groups was modestly attenuated, but remained statistically significant: HR = 1.38, 95% CI = 1.10, 1.73, p = .005. These findings suggest that this functional polymorphism of the 5HTR2C gene is associated with increased risk for CVD mortality and morbidity, but this association is apparently not explained by the association of rs6318 with traditional risk factors or conventional markers of atherosclerotic disease.