Browsing by Author "Werner, Robert"

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    Agreement between Clinical Screening Procedures for Neuropathy in the Feet
    (2012-05) Wang, Yi; Goodrich, Jaclyn M.; Werner, Robert; Gillespie, Brenda; Basu, Niladri; Franzblau, Alfred
    INTRODUCTION: The correlation between monofilament testing, symptom surveys, and electrodiagnostic studies for the diagnosis of axonal polyneuropathy has not been well studied. This investigation was done to assess the agreement between these procedures in a non-random sample of volunteers. METHODS: The procedures evaluated included electrodiagnostic tests of the sural nerve, monofilament testing of the great toe, a symptom survey, and a body diagram. Kappa coefficients and sensitivity and specificity, using nerve conduction as a "gold standard," were used to determine the agreement between various combinations of procedures. RESULTS: Poor agreement (kappa values -0.12-0.44) and sensitivity (sensitivity <30%) were found for all combinations of symptoms and monofilament results in comparison with sural peak latency and amplitude. CONCLUSIONS: Overall, the results demonstrated a low discriminatory power for the screening procedures for identifying persons with impaired sural nerve function. The results highlight the need for further development and evaluation of screening methods for distal neuropathy in population-based studies.
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    Glutathione Enzyme and Selenoprotein Polymorphisms Associate with Mercury Biomarker Levels in Michigan Dental Professionals
    (2011-12) Goodrich, Jaclyn M.; Wang, Yi; Gillespie, Brenda; Werner, Robert; Franzblau, Alfred; Basu, Niladri
    Mercury is a potent toxicant of concern to both the general public and occupationally exposed workers (e.g., dentists). Recent studies suggest that several genes mediating the toxicokinetics of mercury are polymorphic in humans and may influence inter-individual variability in mercury accumulation. This work hypothesizes that polymorphisms in key glutathione synthesizing enzyme, glutathione S-transferase, and selenoprotein genes underlie inter-individual differences in mercury body burden as assessed by analytical mercury measurement in urine and hair, biomarkers of elemental mercury and methylmercury, respectively. Urine and hair samples were collected from a population of dental professionals (n=515), and total mercury content was measured. Average urine (1.06±1.24 microg/L) and hair mercury levels (0.49±0.63 microg/g) were similar to national U.S. population averages. Taqman assays were used to genotype DNA from buccal swab samples at 15 polymorphic sites in genes implicated in mercury metabolism. Linear regression modeling assessed the ability of polymorphisms to modify the relationship between mercury biomarker levels and exposure sources (e.g., amalgams, fish consumption). Five polymorphisms were significantly associated with urine mercury levels (GSTT1 deletion), hair mercury levels (GSTP1-105, GSTP1-114, GSS 5'), or both (SEPP1 3'UTR). Overall, this study suggests that polymorphisms in selenoproteins and glutathione-related genes may influence elimination of mercury in the urine and hair or mercury retention following exposures to elemental mercury (via dental amalgams) and methylmercury (via fish consumption).
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    An investigation of modifying effects of metallothionein single-nucleotide polymorphisms on the association between mercury exposure and biomarker levels
    (2012-04) Wang, Yi; Goodrich, Jaclyn M.; Gillespie, Brenda; Werner, Robert; Basu, Niladri; Franzblau, Alfred
    BACKGROUND: Recent studies have suggested that several genes that mediate mercury metabolism are polymorphic in humans. OBJECTIVE: We hypothesized that single-nucleotide polymorphisms (SNPs) in metallothionein (MT) genes may underlie interindividual differences in mercury biomarker levels. We studied the potential modifying effects of MT SNPs on mercury exposure-biomarker relationships. METHODS: We measured total mercury in urine and hair samples of 515 dental professionals. We also surveyed occupational and personal exposures to dental amalgam and dietary fish consumption, from which daily methylmercury (MeHg) intake was estimated. Log-transformed urine and hair levels were modeled in multivariable linear regression separately against respective exposure surrogates, and the effect modification of 13 MT SNPs on exposure was investigated. RESULTS: The mean mercury levels in urine (1.06 µg/L) and hair (0.51 µg/g) were not significantly different from the U.S. general population (0.95 µg/L and 0.47 µg/g, respectively). The mean estimated daily MeHg intake was 0.084 µg/kg/day (range, 0-0.98 µg/kg/day), with 25% of study population intakes exceeding the current U.S. Environmental Protection Agency reference dose of 0.1 µg/kg/day. Multivariate regression analysis showed that subjects with the MT1M (rs2270837) [corrected] AA genotype (n = 10) or the MT2A (rs10636) CC genotype (n = 42) had lower urinary mercury levels than did those with the MT1M or MT2A GG genotype (n = 329 and 251, respectively) after controlling for exposure and potential confounders. After controlling for MeHg intake, subjects with MT1A (rs8052394) GA and GG genotypes (n = 24) or the MT1M (rs9936741) TT genotype (n = 459) had lower hair mercury levels than did subjects with MT1A AA (n = 113) or MT1M TC and CC genotypes (n = 15), respectively. CONCLUSION: Our findings suggest that some MT genetic polymorphisms may influence mercury biomarker concentrations at levels of exposure relevant to the general population.
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    An Investigation of Modifying Effects of Single Nucleotide Polymorphisms in Metabolism-related Genes on the Relationship between Peripheral Nerve Function and Mercury Levels in Urine and Hair
    (2012-02) Wang, Yi; Goodrich, Jaclyn M.; Werner, Robert; Gillespie, Brenda; Basu, Niladri; Franzblau, Alfred
    Mercury (Hg) is a potent neurotoxicant. We hypothesized that single nucleotide polymorphisms (SNPs) in genes coding glutathione-related proteins, selenoproteins and metallothioneins may modify the relationship of mercury biomarkers with changes in peripheral nerve function. Dental professionals (n=515) were recruited in 2009 and 2010. Sensory nerve function (onset latency, peak latency and amplitude) of the median, ulnar and sural nerves was recorded. Samples of urine, hair and DNA were collected. Covariates related to demographics, nerve function and elemental and methyl-mercury exposure were also collected. Subjects included 244 dentists (47.4%) and 269 non-dentists (52.2%; mostly dental hygienists and dental assistants). The mean mercury levels in urine (1.06 μg/L) and hair (0.51 μg/g) were not significantly different from the US general population (0.95 μg/L and 0.47 μg/g, respectively). In multivariate linear models predicting nerve function adjusting for covariates, only 3 out of a total of 504 models showed stable and statistically significant interaction of SNPs with mercury biomarkers. Overall, given the possibility of false positives, the results suggested little evidence of effect modification of the SNPs on the relationship between mercury biomarkers with peripheral nerve function at exposure levels that are relevant to the general US population.
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    Methylmercury and elemental mercury differentially associate with blood pressure among dental professionals
    (2013-03) Goodrich, Jaclyn M.; Wang, Yi; Gillespie, Brenda; Werner, Robert; Franzblau, Alfred; Basu, Niladri
    Methylmercury-associated effects on the cardiovascular system have been documented though discrepancies exist, and most studied populations experience elevated methylmercury exposures. No paper has investigated the impact of low-level elemental (inorganic) mercury exposure on cardiovascular risk in humans. The purpose of this study was to increase understanding of the association between mercury exposure (methylmercury and elemental mercury) and blood pressure measures in a cohort of dental professionals that experience background exposures to both mercury forms. Dental professionals were recruited during the 2010 Michigan Dental Association Annual Convention. Mercury levels in hair and urine samples were analyzed as biomarkers of methylmercury and elemental mercury exposure, respectively. Blood pressure (systolic, diastolic) was measured using an automated device. Distribution of mercury in hair (mean, range: 0.45, 0.02–5.18 μg/g) and urine (0.94, 0.03–5.54 μg/L) correspond well with the US National Health and Nutrition Examination Survey. Linear regression models revealed significant associations between diastolic blood pressure (adjusted for blood pressure medication use) and hair mercury (n = 262, p = 0.02). Urine mercury results opposed hair mercury in many ways. Notably, elemental mercury exposure was associated with a significant systolic blood pressure decrease (n = 262, p = 0.04) that was driven by the male population. Associations between blood pressure and two forms of mercury were found at exposure levels relevant to the general population, and associations varied according to type of mercury exposure and gender.
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    Relationship of estimated dietary intake of n-3 polyunsaturated fatty acids from fish with peripheral nerve function after adjusting for mercury exposure
    (2013-06-01) Wang, Yi; Goodrich, Jaclyn M.; Werner, Robert; Gillespie, Brenda; Basu, Niladri; Franzblau, Alfred
    BACKGROUND: Some clinical studies have suggested that ingestion of n-3 polyunsaturated fatty acids (PUFA) has neuroprotective effects on peripheral nerve function. However, few epidemiological studies have examined the effect of dietary n-3 PUFA intake from fish consumption on peripheral nerve function, and none have controlled for co-occurrence of methylmercury exposure from fish consumption. OBJECTIVES: We evaluated the effect of estimated dietary n-3 PUFA intake on peripheral nerve function after adjusting for biomarkers of methylmercury and elemental mercury in a convenience sample of 515 dental professionals. METHODS: We measured sensory nerve conduction (peak latency and amplitude) of the median, ulnar and sural nerves and total mercury concentrations in hair and urine samples. We estimated daily intake (mg/day) of the total n-3 PUFA, n-3 docosahexaenoic acid (DHA), and n-3 eicosapentaenoic acid (EPA) based on a self-administrated fish consumption frequency questionnaire. We also collected information on mercury exposure, demographics and other covariates. RESULTS: The estimated median intakes of total n-3 PUFA, n-3 EPA, and n-3 DHA were 447, 105, and 179 mg/day, respectively. The mean mercury concentrations in urine (1.05 μg/L) and hair (0.49 μg/g) were not significantly different from the US general population. We found no consistent association between n-3 PUFA intake and sensory nerve conduction after adjusting for mercury concentrations in hair and urine although some positive associations were observed with the sural nerve. CONCLUSIONS: In a convenience sample of dental professionals, we found little evidence suggesting that dietary intake of n-3 PUFAs from fish has any impact on peripheral nerve function after adjustment for methylmercury exposure from fish and elemental mercury exposure from dental amalgam.