HLA-DPB1 E69 genotype and exposure in beryllium sensitisation and disease.

OBJECTIVES: Human leukocyte antigen-DP beta 1 (HLA-DPB1) with a glutamic acid at the 69th position of the ß chain (E69) genotype and inhalational beryllium exposure individually contribute to risk of chronic beryllium disease (CBD) and beryllium sensitisation (BeS) in exposed individuals. This retrospective nested case-control study assessed the contribution of genetics and exposure in the development of BeS and CBD. METHODS: Workers with BeS (n=444), CBD (n=449) and beryllium-exposed controls (n=890) were enrolled from studies conducted at nuclear weapons and primary beryllium manufacturing facilities. Lifetime-average beryllium exposure estimates were based on workers' job questionnaires and historical and industrial hygienist exposure estimates, blinded to genotype and case status. Genotyping was performed using sequence-specific primer-PCR. Logistic regression models were developed allowing for over-dispersion, adjusting for workforce, race, sex and ethnicity. RESULTS: Having no E69 alleles was associated with lower odds of both CBD and BeS; every additional E69 allele increased odds for CBD and BeS. Increasing exposure was associated with lower odds of BeS. CBD was not associated with exposure as compared to controls, yet the per cent of individuals with CBD versus BeS increased with increasing exposure. No evidence of a gene-by-exposure interaction was found for CBD or BeS. CONCLUSIONS: Risk of CBD increases with E69 allele frequency and increasing exposure, although no gene by environment interaction was found. A decreased risk of BeS with increasing exposure and lack of exposure response in CBD cases may be due to the limitations of reconstructed exposure estimates. Although reducing exposure may not prevent BeS, it may reduce CBD and the associated health effects, especially in those carrying E69 alleles.

The CHARGE study: an assessment of parental occupational exposures and autism spectrum disorder.

OBJECTIVES: The aim of this study is to determine if parental occupational exposure to 16 agents is associated with autism spectrum disorder (ASD). METHODS: Demographic, health and parental occupational data were collected as part of the CHildhood Autism Risks from Genetics and Environment study. The workplace exposure assessment was conducted by two experienced industrial hygienists for the parents of 537 children with ASD and 414 typically developing (TD) children. For each job, frequency and intensity of 16 agents were assessed and both binary and semi-quantitative cumulative exposure variables were derived. Logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) to assess associations between parental occupational exposures 3 months pre-pregnancy until birth. RESULTS: The OR of ASD in the children of mothers exposed to any solvents was 1.5 times higher than the mothers of TD children (95% CI=1.01-2.23). Cumulative exposure indicated that the OR associated with a moderate level of solvent exposure in mothers was 1.85 (95% CI=1.09, 3.15) for children with ASD compared with TD children. No other exposures were associated with ASD in mothers, fathers or the parents combined. CONCLUSION: Maternal occupational exposure to solvents may increase the risk for ASD. These results are consistent with a growing body of evidence indicating that environmental and occupational exposures may be associated with ASD. Future research should consider specific types of solvents, larger samples and/or different study designs to evaluate other exposures for potential associations with ASD.

The effect of social support, gratitude, resilience and satisfaction with life on depressive symptoms among police officers following Hurricane Katrina.

BACKGROUND: Police officers in the New Orleans geographic area faced a number of challenges following Hurricane Katrina. AIM: This cross-sectional study examined the effect of social support, gratitude, resilience and satisfaction with life on symptoms of depression. METHOD: A total of 86 male and 30 female police officers from Louisiana participated in this study. Ordinary least-square (OLS) regression mediation analysis was used to estimate direct and indirect effects between social support, gratitude, resilience, satisfaction with life and symptoms of depression. All models were adjusted for age, alcohol intake, military experience and an increase in the number of sick days since Hurricane Katrina. RESULTS: Mean depressive symptom scores were 9.6 ± 9.1 for females and 10.9 ± 9.6 for males. Mediation analyses indicates that social support and gratitude are directly associated with fewer symptoms of depression. Social support also mediated the relationships between gratitude and depression, gratitude and satisfaction with life, and satisfaction with life and depression. Similarly, resilience mediated the relationship between social support and fewer symptoms of depression. CONCLUSION: Social support, gratitude and resilience are associated with higher satisfaction with life and fewer symptoms of depression. Targeting and building these factors may improve an officer's ability to address symptoms of depression.

Stressful life events and posttraumatic growth among police officers: A cross-sectional study.

Police officers often continue to face numerous threats and stressors in the aftermath of a disaster. To date, posttraumatic growth (PTG) has been studied primarily in the context of significant trauma; thus, it is not known whether stressful life events are associated with PTG. This study investigated the development of PTG among 113 police officers working in the New Orleans area following Hurricane Katrina. Hierarchical regression was used to evaluate if gratitude, social support, and satisfaction with life moderated the relationship between stressful life events (as measured by the total life stress score) and PTG, after adjustment for age, sex, race, level of involvement in Hurricane Katrina, and alcohol intake. Results indicate that stressful life events are independently associated with PTG. Gratitude, satisfaction with life, and social support were seen to moderate this relationship; as stressful life events increased so too did PTG-particularly among officers with higher levels of gratitude (B = 0.002, p ≤ .05), satisfaction with life (B = 0.002, p ≤ .05), and social support (B = 0.001, p ≤ .05). These findings suggest that promoting satisfaction with life, interpersonal support, and gratitude may be beneficial to those who are regularly at risk of trauma exposure.

Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder.

BACKGROUND: Maternal folic acid (FA) protects against developmental toxicity from certain environmental chemicals. OBJECTIVE: We examined combined exposures to maternal FA and pesticides in relation to autism spectrum disorder (ASD). METHODS: Participants were California children born from 2000-2007 who were enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) case-control study at age 2-5 y, were clinically confirmed to have ASD (n=296) or typical development (n=220), and had information on maternal supplemental FA and pesticide exposures. Maternal supplemental FA and household pesticide product use were retrospectively collected in telephone interviews from 2003-2011. High vs. low daily FA intake was dichotomized at 800µg (median). Mothers' addresses were linked to a statewide database of commercial applications to estimate agricultural pesticide exposure. RESULTS: High FA intake (≥800µg) during the first pregnancy month and no known pesticide exposure was the reference group for all analyses. Compared with this group, ASD was increased in association with <800µg FA and any indoor pesticide exposure {adjusted odds ratio [OR]=2.5 [95% confidence interval (CI): 1.3, 4.7]} compared with low FA [OR=1.2 (95% CI: 0.7, 2.2)] or indoor pesticides [OR=1.7 (95% CI: 1.1, 2.8)] alone. ORs for the combination of low FA and regular pregnancy exposure (≥6 mo) to pet pesticides or to outdoor sprays and foggers were 3.9 (95% CI: 1.4, 11.5) and 4.1 (95% CI: 1.7, 10.1), respectively. ORs for low maternal FA and agricultural pesticide exposure 3 mo before or after conception were 2.2 (95% CI: 0.7, 6.5) for chlorpyrifos, 2.3 (95% CI: 0.98, 5.3) for organophosphates, 2.1 (95% CI: 0.9, 4.8) for pyrethroids, and 1.5 (95% CI: 0.5, 4.8) for carbamates. Except for carbamates, these ORs were approximately two times greater than those for either exposure alone or for the expected ORs for combined exposures under multiplicative or additive models. CONCLUSIONS: In this study population, associations between pesticide exposures and ASD were attenuated among those with high versus low FA intake during the first month of pregnancy. Confirmatory and mechanistic studies are needed. https://doi.org/10.1289/EHP604.

Resilience mediates the relationship between social support and post-traumatic stress symptoms in police officers.

OBJECTIVE: Police officers in the New Orleans geographic area faced a number of challenges following Hurricane Katrina in 2005. DESIGN: This cross-sectional study examined gratitude, resilience, and satisfaction with life as mediators in the association between social support and post-traumatic stress disorder (PTSD) symptoms in 82 male and 31 female police officers. The Gratitude Questionnaire, Connor-Davidson Resilience Scale, Satisfaction with Life Scale, and the Interpersonal Support Evaluation List were used to measure gratitude, resilience, satisfaction with life, and social support, respectively. PTSD symptoms were measured using the PTSD Checklist-Civilian (PCL-C). Ordinary least square regression mediation analysis was used to estimate direct and indirect effects among gratitude, resilience, satisfaction with life, social support, and PTSD symptoms. All models were adjusted for age, alcohol, race, and previous military experience. RESULTS: Mean PCL-C symptoms were 29.1 (standard deviation [SD] = 14.4) for females and 27.9 (SD = 12.1) for males. There was no direct relationship between social support and PTSD symptoms (c9 = -0.041; 95% confidence interval [CI] = -0.199, 0.117) independent of the indirect effect through resilience (effect = -0.038; 95%CI = -0.099, -0.002). Neither gratitude (effect = -0.066; 95% CI = -0.203, 0.090) nor satisfaction with life (effect = -0.036, 95% CI = -0.131, 0.046) contribute to the indirect effect. CONCLUSIONS: These results indicate that resilience mediates the relationship between social support and symp-toms of PTSD. Targeting social support and resilience in officers may facilitate reduction of PTSD symptoms.

Association of peritraumatic dissociation with symptoms of depression and posttraumatic stress disorder.

AIM: In this study, we evaluated whether peritraumatic dissociation (PD) was associated with symptoms of depression and posttraumatic stress disorder (PTSD), and whether this association was modified by trauma prior to police work. METHOD: Symptoms of depression, PTSD, peritraumatic dissociative experience (PDE), and trauma prior to police work were measured using the Center for Epidemiologic Studies Depression scale, PTSD Checklist-Civilian, PDE questionnaire, and the Brief Trauma questionnaire, respectively, in 328 police officers. Separate regression models were used to assess if either symptoms of depression or PTSD were associated with PD stratified by prior trauma. Means were adjusted for race, number of drinks per week, and smoking. RESULTS: PD was associated with symptoms of PTSD and depression (ß = 0.65, p < .001 and ß = 0.27, p < .001, respectively). PD was positively associated with symptoms of PTSD regardless of prior trauma (ß = 0.61, p < .001(without prior trauma), 0.75, p < .001 (with prior trauma). In contrast to PTSD, depression symptoms were significantly associated with PD scores in individuals with prior trauma (ß = 0.47, p < .001), but not in individuals without prior trauma (ß = 0.13, p = .165). LIMITATIONS: This is a cross-sectional study. Outcomes were obtained via self-report and were not clinically diagnosed. Aspects of both the trauma event as well as the symptoms and severity of PD may have introduced recall bias. CONCLUSION: These results add to the literature indicating that PD plays a role in symptoms of PTSD and depression and how prior trauma may modify this relationship. (PsycINFO Database Record

Research to Practice Implications of High-Risk Genotypes for Beryllium Sensitization and Disease.

OBJECTIVE: Beryllium workers may better understand their genetic susceptibility to chronic beryllium disease (CBD) expressed as population-based prevalence, rather than odds ratios from case-control studies. METHODS: We calculated CBD prevalences from allele-specific DNA sequences of 853 workers for Human Leukocyte Antigen (HLA)-DPB1 genotypes and groups characterized by number of E69-containing alleles and by calculated surface electronegativity of HLA-DPB1. RESULTS: Of 18 groups of at least 10 workers with specific genotypes, CBD prevalence was highest, 72.7%, for the HLA-DPB102:01:02/DPB117:01 genotype. Population-based grouped genotypes with two E69 alleles wherein one allele had -9 surface charge had a beryllium sensitization (BeS) of 52.6% and a CBD prevalence of 42.1%. CONCLUSIONS: The high CBD and BeS prevalences associated with -9-charged E69 alleles and two E69s suggest that workers may benefit from knowing their genetic susceptibility in deciding whether to avoid future beryllium exposure.

Positive psychological factors are associated with lower PTSD symptoms among police officers: post Hurricane Katrina.

Following Hurricane Katrina, police officers in the New Orleans geographic area faced a number of challenges. This cross-sectional study examined the association between resilience, satisfaction with life, gratitude, posttraumatic growth, and symptoms of posttraumatic stress disorder in 84 male and 30 female police officers from Louisiana. Protective factors were measured using the Connor-Davidson Resilience scale, Satisfaction with Life Scale, the Gratitude Questionnaire, and the Posttraumatic Growth inventory. Symptoms of posttraumatic stress disorder were measured using the Posttraumatic Stress Disorder Checklist--Civilian (PCL-C). Potential associations were measured using linear regression and analysis of variance. Models were adjusted for age, sex, race, education, and alcohol. Mean PCL-C symptoms were 29.5 ± 14.5 for females and 27.8 ± 12.1 for males. Adjusted mean levels of PCL-C symptoms significantly decreased as quartiles of resilience (p < .001), satisfaction with life (p < .001), and gratitude (p < .001) increased. In contrast, PCL-C symptoms were not associated with posttraumatic growth in this sample. These results indicate that positive factors such as resilience, satisfaction with life, and gratitude may help mitigate symptoms of posttraumatic stress disorder. To further explore these relationships, longitudinal follow-up in a larger population would be of interest.

Associations between protective factors and psychological distress vary by gender: the Buffalo Cardio-Metabolic Occupational Police Stress Study.

Previous research by this group identified gender interactions between some protective factors and psychological distress in police officers. This study extends this result to include a larger sample of police officers and a more comprehensive list of protective factors. These results confirm the conclusion that the commitment dimension of hardiness appears to have a stronger protective association with psychological distress among women. Furthermore, an avoidant coping style appears to be somewhat more positively associated with psychological distress among women. The personality trait of openness was also positively associated more strongly with PTSD symptoms in women than in men, while the trait of agreeableness was significantly protective in women and not in men. Hostility was generally positively associated with psychological distress with stronger association for PTSD symptoms and hostility in women.

Chronic beryllium disease, HLA-DPB1, and the DP peptide binding groove.

Multiple epidemiologic studies demonstrate associations between chronic beryllium disease (CBD), beryllium sensitization (BeS), and HLA-DPB1 alleles with a glutamic acid residue at position 69 (E69). Results suggest that the less-frequent E69 variants (non-*0201/*0202 alleles) might be associated with greater risk of CBD. In this study, we sought to define specific E69-carrying alleles and their amino acid sequences in the DP peptide binding groove, as well as their relationship to CBD and BeS risk, using the largest case control study to date. We enrolled 502 BeS/CBD subjects and 653 beryllium-exposed controls from three beryllium industries who gave informed consent for participation. Non-Hispanic white cases and controls were frequency-matched by industry. HLA-DPB1 genotypes were determined using sequence-specific primer PCR. The E69 alleles were tested for association with disease individually and grouped by amino acid structure using logistic regression. The results show that CBD cases were more likely than controls to carry a non-*02 E69 allele than an *02 E69, with odds ratios (95% confidence interval) ranging from 3.1 (2.1-4.5) to 3.9 (2.6-5.9) (p < 0.0001). Polymorphic amino acids at positions 84 and 11 were associated with CBD: DD versus GG, 2.8 (1.8-4.6), p < 0.0001; GD versus GG, 2.1 (1.5-2.8), p < 0.0001; LL versus GG, 3.2 (1.8-5.6), p < 0.0001; GL versus GG, 2.8 (2.1-3.8), p < 0.0001. Similar results were found within the BeS group and CBD/BeS combined group. We conclude that the less frequent E69 alleles confer more risk for CBD than does *0201. Recent studies examining how the composition and structure of the binding pockets influence peptide binding in MHC genes, as well of studies showing the topology of the TCR to likely bind DPB1 preferentially, give plausible biological rationale for these findings.

Metabolic syndrome and sleep duration in police officers.

OBJECTIVES: To examine associations for sleep quality and quantity with metabolic syndrome (MS) and its five components in police officers. PATIENTS OR PARTICIPANTS: The study population consisted of 98 randomly selected officers (39 women and 59 men) for whom MS and sleep data were available. METHODS: Sleep duration (categorized as short < 6 hours, long ≥ 6 hours) for the past week and quality of sleep were collected by interviewer-administered questionnaires. MS was assessed using standard criteria. Generalized linear models were used to assess associations between sleep duration or sleep quality and MS, and the mean number of MS components. RESULTS: Metabolic syndrome was present in 22.0% and 2.6% of the male and female officers, respectively. Women with short sleep had a significantly higher mean number of MS components (mean=1.43) than those with longer sleep (mean=0.81, p=0.0316). Officers who stopped breathing during the night had more MS components (mean=2.43) compared to those who did not (mean =1.13, p=0.0206). CONCLUSIONS: Sleep duration and quality were associated with the mean number of MS components, particularly in women. Future research should examine these associations prospectively, in a larger cohort, exploring possible gender differences.

Parental occupational exposures and autism spectrum disorder.

Both self-report and industrial hygienist (IH) assessed parental occupational information were used in this pilot study in which 174 families (93 children with ASD and 81 unaffected children) enrolled in the Childhood Autism Risks from Genetics and Environment study participated. IH results indicated exposures to lacquer, varnish, and xylene occurred more often in the parents of children with ASD compared to the parents of unaffected children. Parents of children with ASD were more likely to report exposures to asphalt and solvents compared to parents of unaffected children. This study was limited by the small sample size, but results suggest that workplace exposures to some chemicals may be important in the etiology of ASD and deserve further investigation.

C-reactive protein, interleukin-6, and posttraumatic stress disorder symptomology in urban police officers.

Our aim was to examine the relationship between the level of the inflammatory markers, C-reactive protein (CRP) and interleukin-6 (IL-6), and posttraumatic stress disorder (PTSD) symptomology in a random sample of 115 police officers. CRP was measured in citrated plasma using a particle enhanced immunonepholometric assay and IL-6 was measured in serum with a solid-phase quantitative sandwich ELISA. The presence of high PTSD symptomology was defined as having an Impact of Event Scale score (IES) of ≥ 26 compared to<26 (low PTSD symptomology). 28% of the officers had high PTSD symptomology. Mean levels of CRP and IL-6 did not differ significantly between officers with high PTSD symptomology and those with low symptomology (CRP: 0.76 mg/l vs. 0.97 mg/l; IL-6: 2.03 pg/ml vs. 1.74 pg/ml). We found no association of CRP and IL-6 levels with PTSD symptomology. This study was limited by sample size and its cross-sectional study design. A lack of association may occur if either CRP or IL-6 is elevated only at the onset of PTSD symptomology, or if inflammation is related to specific key components that define PTSD. Further research examining these relationships in a larger population may be worthwhile.

Association between IL-1A single nucleotide polymorphisms and chronic beryllium disease and beryllium sensitization.

OBJECTIVE: To determine if single nucleotide polymorphisms (SNPs) in interleukin (IL) IL-1A, IL-1B, IL-1RN, IL-2, IL-9, and IL-9R were associated with chronic beryllium disease (CBD) and beryllium sensitization (BeS). METHODS: Forty SNPs in six IL genes were evaluated in 85 individuals with CBD, 61 individuals with BeS, and 730 individuals without BeS or CBD (nonsensitized) using a 5' nuclease polymerase chain reaction assay. Logistic regression was used to evaluate the association between IL SNPs, CBD, and BeS, adjusting for plant-site and HLA-DPB1Glu69 in additive, dominant, and recessive inheritance models. RESULTS: IL-1A-1142, IL-1A-3769, and IL-1A-4697 were significantly associated with CBD in both the additive and dominant models compared to individuals with BeS or the nonsensitized. CONCLUSIONS: These results indicate that genetic variations in the IL-1A gene may play a role in the development of CBD but not BeS.

Telomere length, current perceived stress, and urinary stress hormones in women.

Telomeres are repetitive DNA sequences that cap and protect the ends of chromosomes; critically short telomeres may lead to cellular senescence or carcinogenic transformation. Previous findings suggest a link between psychosocial stress, shorter telomeres, and chronic disease risk. This cross-sectional study examined relative telomere length in relation to perceived stress and urinary stress hormones in a sample of participants (n = 647) in the National Institute of Environmental Health Sciences Sister Study, a cohort of women ages 35 to 74 years who have a sister with breast cancer. Average leukocyte telomere length was determined by quantitative PCR. Current stress was assessed using the Perceived Stress Scale and creatinine-adjusted neuroendocrine hormones in first morning urines. Linear regression models estimated differences in telomere length base pairs (bp) associated with stress measures adjusted for age, race, smoking, and obesity. Women with higher perceived stress had somewhat shorter telomeres [adjusted difference of -129bp for being at or above moderate stress levels; 95% confidence interval (CI), -292 to 33], but telomere length did not decrease monotonically with higher stress levels. Shorter telomeres were independently associated with increasing age (-27bp/year), obesity, and current smoking. Significant stress-related differences in telomere length were seen in women ages 55 years and older (-289bp; 95% CI, -519 to -59), those with recent major losses (-420bp; 95% CI, -814 to -27), and those with above-average urinary catecholamines (e.g., epinephrine: -484bp; 95% CI, -709 to -259). Although current perceived stress was only modestly associated with shorter telomeres in this broad sample of women, our findings suggest the effect of stress on telomere length may vary depending on neuroendocrine responsiveness, external stressors, and age.

Hardiness and psychological distress in a cohort of police officers.

Since police officers are frequently exposed to high stress situations, individual differences in the response to stress and trauma are of interest. We examined the association of hardiness components (commitment, control and challenge) with depression, posttraumatic stress disorder (PTSD) symptoms, and symptoms of general psychological distress in police officers. The random sample included 105 officers (40 women and 65 men) from the Buffalo Cardio-Metabolic Police Stress (BCOPS) study baseline visit. Components of hardiness were measured using a 15-item hardiness scale. Depressive symptoms were measured using the Center for Epidemiological Studies Depression scale (CES-D), PTSD symptoms were measured using the impact of events scale (IES), and symptoms of general psychological distress were measured using the Brief Symptoms Inventory (BSI). Associations were assessed using linear regression analysis. Models were adjusted for age, education and marital status. Because of significant gender interactions, analyses were stratified by gender. The hardiness control dimension was significantly and negatively associated with CES-D for both genders but was not associated with IES. Hardiness commitment was significantly and negatively associated with both CES-D and IES in women. Men had negative but non-significant associations for commitment with CES-D and IES. Hardiness commitment was negatively associated with the overall BSI score for both men and women but the association was only significant for men, though the strength of the association was stronger for women. This is likely a result of the impact of the smaller sample size for women. The magnitude of gender differences in these associations shows that for depressive and PTSD symptoms, the commitment dimension of hardiness may be more protective in female police officers than in male officers.

Impact of negatively charged patches on the surface of MHC class II antigen-presenting proteins on risk of chronic beryllium disease.

Chronic beryllium disease (CBD) is a granulomatous lung disease that occurs primarily in workers who are exposed to beryllium dust or fumes. Although exposure to beryllium is a necessary factor in the pathobiology of CBD, alleles that code for a glutamic acid residue at the 69th position of the HLA-DPbeta1 gene have previously been found to be associated with CBD. To date, 43 HLA-DPbeta1 alleles that code for glutamic acid 69 (E69) have been described. Whether all of these E69 coding alleles convey equal risk of CBD is unknown. The present study demonstrates that, on the one hand, E69 alleloforms of major histocompatibility complex class II antigen-presenting proteins with the greatest negative surface charge convey the highest risk of CBD, and on the other hand, irrespective of allele, they convey equal risk of beryllium sensitization (BeS). In addition, the data suggest that the same alleles that cause the greatest risk of CBD are also important for the progression from BeS to CBD. Alleles convey the highest risk code for E26 in a constant region and for E69, aspartic acid 55 (D55), E56, D84 and E85 in hypervariable regions of the HLA-DPbeta1 chain. Together with the calculated high binding affinities for beryllium, these results suggest that an adverse immune response, leading to CBD, is triggered by chemically specific metal-protein interactions.

TNF-alpha polymorphisms in chronic beryllium disease and beryllium sensitization.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is a potent cytokine involved in normal immune functions. The aim of this study was to investigate if there is an association between chronic beryllium disease or beryllium sensitization and two variants of the TNF-alpha gene located at -308 and -238 called TNF-alpha-308*02 and TNF-alpha-238*02. METHODS: TNF-alpha-308 and TNF-alpha-238 genotyping was conducted in a large, population-based cohort consisting of 886 beryllium workers (92 individuals with chronic beryllium disease, 64 who were beryllium sensitized, and 730 individuals without sensitization or disease). RESULTS: The odds of chronic beryllium disease in the presence of at least one TNF-alpha-308*02 or TNF-alpha-238*02 allele was not significant (OR=1.0; 95% CI=0.7, 1.7 and OR=0.8; 95% CI=0.4, 1.6). This was true regardless of whether a worker was homozygous or heterozygous for TNF-alpha-308*02 or TNF-alpha-238*02. Similarly, neither allele was associated with sensitization (P>0.05). CONCLUSIONS: Unlike an earlier report, there was no association between these specific TNF-alpha alleles and either chronic beryllium disease or sensitization to beryllium.