Coping with oil spills: oil exposure and anxiety among residents of Gulf Coast states after the Deepwater Horizon Oil Spill.

In April 2010, a fatal explosion on the Deepwater Horizon drilling rig in the Gulf of Mexico resulted in the largest marine oil spill in history. This research describes the association of oil exposure with anxiety after the Deepwater Horizon Oil Spill and evaluates effect modification by self-mastery, emotional support and cleanup participation. To assess the impacts of the Deepwater Horizon Oil Spill, the Centers for Disease Control and Prevention (CDC) conducted the Gulf States Population Survey (GSPS), a random-digit-dial telephone cross-sectional survey completed between December 2010 and December 2011 with 38,361 responses in four different Gulf Coast states: Louisiana, Florida, Alabama and Mississippi. Anxiety severity was measured using the Generalised Anxiety Disorder (GAD) symptom inventory. We used Tobit regression to model underlying anxiety as a function of oil exposure and hypothesised effect modifiers, adjusting for socio-demographics. Latent anxiety was higher among those with direct contact with oil than among those who did not have direct contact with oil in confounder-adjusted models [ß = 2.84, 95% confidence interval (CI): 0.78, 4.91]. Among individuals with direct contact with oil, there was no significant interaction between participating in cleanup activities and emotional support for anxiety (p = 0.20). However, among those with direct contact with oil, in confounder-adjusted models, participation in oil spill cleanup activities was associated with lower latent anxiety (ß = -3.55, 95% CI: -6.15, -0.95). Oil contact was associated with greater anxiety, but this association appeared to be mitigated by cleanup participation.

Exposure patterns among Coast Guard responders to the Deepwater Horizon Oil Spill: A latent class analysis.

Background: The Deepwater Horizon Oil Spill was an environmental crisis for which multiple groups, including the United States Coast Guard (USCG), provided emergency response services. A cohort of 5,665 USCG oil spill responders completed postdeployment surveys eliciting information on a variety of topics, including oil spill-related exposures and experiences. Our objective was to determine the most common exposure patterns among USCG responders. Methods: We used latent class analysis based on six indicator variables reflecting different aspects of the responders' experiences: exposure to oil, exposure to engine exhaust fumes or carbon monoxide, hand sanitizer use, sunblock use, mosquito bites, and level of anxiety. We validated our interpretation of these latent classes using ancillary variables. Results: The model distinguished four distinct exposure profiles, which we interpreted as "low overall exposure" (prevalence estimate = 0.18), "low crude oil/exhaust and moderate time outdoors/anxiety (prevalence estimate = 0.18), "high crude oil/exhaust and moderate time outdoors/anxiety" (prevalence estimate = 0.25), and "high overall exposure" (prevalence estimate = 0.38). The validation analysis was consistent with our interpretation of the latent classes. Conclusions: The exposure patterns identified in this analysis can help inform future studies of the health impacts of exposure mixtures among USCG oil spill responders.

The association of arsenic exposure and arsenic metabolism with all-cause, cardiovascular and cancer mortality in the Strong Heart Study.

The effect of low-moderate levels of arsenic exposure and of arsenic metabolism on mortality remains uncertain. We used data from a prospective cohort study in 3600 men and women aged 45 to 75 years living in Arizona, Oklahoma, and North and South Dakota. The biomarker of inorganic arsenic exposure was the sum of urine inorganic (iAs), monomethylated (MMA) and dimethylated (DMA) arsenic compounds (Æ©As) at baseline. The proportions of urine iAs, MMA and DMA over the Æ©iAs, expressed as iAs%, MMA%, and DMA%, respectively, were used as biomarkers of arsenic metabolism. Arsenic exposure and arsenic metabolism were associated with all-cause, cardiovascular, and cancer mortality. For each interquartile range (IQR) increase in Æ©As (12.5 µg/L, overall range 0.7-194.1 µg/L), the adjusted hazard ratios (aHRs) were 1.28 (95% CI 1.16-1.41) for all-cause mortality, 1.28 (1.08-1.52) for cardiovascular mortality and 1.15 (0.92-1.44) for cancer mortality. The aHR for mortality for each IQR increase in MMA%, when iAs% is decreasing, was 1.52 (95% CI 1.16-1.99) for cardiovascular disease, 0.73 (0.55-0.98) for cancer, and 1.03 (0.90-1.19) for all-cause mortality. These findings at low-moderate levels of arsenic exposure highlight the need to implement public health measures to protect populations from involuntary arsenic exposure and for research to advance the biological and clinical understanding of arsenic-related health effects in general populations.

Screening for Predictors of Chronic Ciguatera Poisoning: An Exploratory Analysis among Hospitalized Cases from French Polynesia.

Ciguatera poisoning is a globally occurring seafood disease caused by the ingestion of marine products contaminated with dinoflagellate produced neurotoxins. Persistent forms of ciguatera, which prove to be highly debilitating, are poorly studied and represent a significant medical issue. The present study aims to better understand chronic ciguatera manifestations and identify potential predictive factors for their duration. Medical files of 49 patients were analyzed, and the post-hospitalization evolution of the disease assessed through a follow-up questionnaire. A rigorous logistic lasso regression model was applied to select significant predictors from a list of 37 patient characteristics potentially predictive of having chronic symptoms. Missing data were handled by complete case analysis, and a survival analysis was implemented. All models used standardized variables, and multiple comparisons in the survival analyses were handled by Bonferroni correction. Among all studied variables, five significant predictors of having symptoms lasting ≥3 months were identified: age, tobacco consumption, acute bradycardia, laboratory measures of urea, and neutrophils. This exploratory, hypothesis-generating study contributes to the development of ciguatera epidemiology by narrowing the list from 37 possible predictors to a list of five predictors that seem worth further investigation as candidate risk factors in more targeted studies of ciguatera symptom duration.

Metal biomarker mixtures and blood pressure in the United States: cross-sectional findings from the 1999-2006 National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: The objective of this study was to identify conditional relationships between multiple metal biomarkers that predict systolic and diastolic blood pressure in the non-institutionalized United States adult population below the age of 60. METHODS: We used inorganic exposure biomarker data and blood pressure data from three cycles (1999-2004) of the National Health and Nutrition Examination Survey (NHANES) to construct regression trees for blood pressure among adults ages 20-60 (adjusted for age, sex, body mass index, race, and smoking status) to identify predictors of systolic (SBP) and diastolic blood pressure (DBP). We also considered relationships among non-Hispanic black, Mexican-American, and white adults separately. RESULTS: The following metal exposure biomarkers were conditionally predictive of SBP and/or DBP in the full sample: antimony (Sb), barium (Ba), cadmium (Cd), cesium (Cs), lead (Pb), tungsten (W) and molybdenum (Mo). The highest average SBP (> 120 mmHg) was observed among those with low Sb (≤ 0.21 µg/dL) high Cd (> 0.22 µg/g creatinine) and high Pb (> 2.55 µg/dL) biomarkers. Those with the highest average DBP had high urinary W levels (> 0.10 µg/g creatinine) in combination with either urinary Sb > 0.17 µg/g creatinine or those with urinary Sb ≤ 0.17 µg/g creatinine, but with high blood Pb levels (> 1.35 µg/dL). Predictors differed by ethnicity, with Cd as the main predictor of SBP among non-Hispanic black adults, and Pb not selected by the algorithm as a predictor of SBP among non-Hispanic white adults. CONCLUSIONS: Combinations of metal biomarkers have different apparent relationships with blood pressure. Additional research in toxicological experimental models and in epidemiological studies is warranted to evaluate the suggested possible toxicological interactions between Sb, Cd, and Pb; and between W, Sb, and Pb; for cardiovascular (e.g., blood pressure) health. We also think future epidemiological research on inorganic exposure sets in relation to health outcomes like blood pressure might benefit from stratification by race and ethnicity.

Past Sodium Intake, Contemporary Sodium Intake, and Cardiometabolic Health in Southwest Coastal Bangladesh.

Background We compared the relationship of past and contemporary sodium (Na) intake with cardiometabolic biomarkers. Methods and Results A total of 1191 participants' data from a randomized controlled trial in coastal Bangladesh were analyzed. Participants provided 24-hour urine Na (24UNa) data for 5 monthly visits. Their fasting blood glucose, total cholesterol, triglycerides, high-density lipoprotein, blood pressure, and 24-hour urine protein were measured at the fifth visit. Participants' mean 24UNa over the first 4 visits was the past Na, and 24UNa of the fifth visit was the contemporary Na intake. We estimated the prevalence ratios of elevated cardiometabolic biomarkers and metabolic syndrome across 24UNa tertiles by multilevel logistic regression using participant-, household-, and community-level random intercepts. Models were adjusted for age, sex, body mass index, smoking, physical activity, alcohol consumption, sleep hours, religion, and household wealth. Compared with participants in tertile 1 of past urine Na, those in tertile 3 had 1.46 (95% CI, 1.08-1.99) times higher prevalence of prediabetes or diabetes mellitus, 5.49 (95% CI, 2.73-11.01) times higher prevalence of large waist circumference, and 1.60 (95% CI, 1.04-2.46) times higher prevalence of metabolic syndrome. Compared with participants in tertile 1 of contemporary urine Na, those in tertile 3 had 1.93 (95% CI, 1.24-3.00) times higher prevalence of prediabetes or diabetes mellitus, 3.14 (95% CI, 1.45-6.83) times higher prevalence of proteinuria, and 2.23 (95% CI, 1.34-3.71) times higher prevalence of large waist circumference. Conclusions Both past and contemporary Na intakes were associated with higher cardiometabolic disease risk.

Locus-Specific Differential DNA Methylation and Urinary Arsenic: An Epigenome-Wide Association Study in Blood among Adults with Low-to-Moderate Arsenic Exposure.

BACKGROUND: Chronic exposure to arsenic (As), a human toxicant and carcinogen, remains a global public health problem. Health risks persist after As exposure has ended, suggesting epigenetic dysregulation as a mechanistic link between exposure and health outcomes. OBJECTIVES: We investigated the association between total urinary As and locus-specific DNA methylation in the Strong Heart Study, a cohort of American Indian adults with low-to-moderate As exposure [total urinary As, mean (±SD) µg/g creatinine: 11.7 (10.6)]. METHODS: DNA methylation was measured in 2,325 participants using the Illumina MethylationEPIC array. We implemented linear models to test differentially methylated positions (DMPs) and the DMRcate method to identify regions (DMRs) and conducted gene ontology enrichment analysis. Models were adjusted for estimated cell type proportions, age, sex, body mass index, smoking, education, estimated glomerular filtration rate, and study center. Arsenic was measured in urine as the sum of inorganic and methylated species. RESULTS: In adjusted models, methylation at 20 CpGs was associated with urinary As after false discovery rate (FDR) correction (FDR< 0.05). After Bonferroni correction, 5 CpGs remained associated with total urinary As (pBonferroni<0.05), located in SLC7A11, ANKS3, LINGO3, CSNK1D, ADAMTSL4. We identified one DMR on chromosome 11 (chr11:2,322,050-2,323,247), annotated to C11orf2; TSPAN32 genes. DISCUSSION: This is one of the first epigenome-wide association studies to investigate As exposure and locus-specific DNA methylation using the Illumina MethylationEPIC array and the largest epigenome-wide study of As exposure. The top DMP was located in SLC7A11A, a gene involved in cystine/glutamate transport and the biosynthesis of glutathione, an antioxidant that may protect against As-induced oxidative stress. Additional DMPs were located in genes associated with tumor development and glucose metabolism. Further research is needed, including research in more diverse populations, to investigate whether As-related DNA methylation signatures are associated with gene expression or may serve as biomarkers of disease development. https://doi.org/10.1289/EHP6263.

Potentially Heterogeneous Cross-Sectional Associations of Seafood Consumption with Diabetes and Glycemia in Urban South Asia.

Aims: In this study, we aimed to estimate cross-sectional associations of fish or shellfish consumption with diabetes and glycemia in three South Asian mega-cities. Methods: We analyzed baseline data from 2010-2011 of a cohort (n = 16,287) representing the population ≥20 years old that was neither pregnant nor on bedrest from Karachi (unweighted n = 4017), Delhi (unweighted n = 5364), and Chennai (unweighted n = 6906). Diabetes was defined as self-reported physician-diagnosed diabetes, fasting plasma glucose ≥126 mg/dL (7.0 mmol/L), or glycated hemoglobin A1c (HbA1c) ≥6.5% (48 mmol/mol). We estimated adjusted and unadjusted odds ratios for diabetes using survey estimation logistic regression for each city, and differences in glucose and HbA1c using survey estimation linear regression for each city. Adjusted models controlled for age, gender, body mass index, waist-height ratio, sedentary lifestyle, educational attainment, tobacco use, an unhealthy diet index score, income, self-reported physician diagnosis of high blood pressure, and self-reported physician diagnosis of high cholesterol. Results: The prevalence of diabetes was 26.7% (95% confidence interval: 24.8, 28.6) in Chennai, 36.7% (32.9, 40.5) in Delhi, and 24.3% (22.0, 26.6) in Karachi. Fish and shellfish were consumed more frequently in Chennai than in the other two cities. In Chennai, the adjusted odds ratio for diabetes, comparing more than weekly vs. less than weekly fish consumption, was 0.81 (0.61, 1.08); in Delhi, it was 1.18 (0.87, 1.58), and, in Karachi, it was 1.30 (0.94, 1.80). In Chennai, the adjusted odds ratio of prevalent diabetes among persons consuming shellfish more than weekly versus less than weekly was 1.08 (95% CI: 0.90, 1.30); in Delhi, it was 1.35 (0.90, 2.01), and, in Karachi, it was 1.68 (0.98, 2.86). Conclusions: Both the direction and the magnitude of association between seafood consumption and glycemia may vary by city. Further investigation into specific locally consumed seafoods and their prospective associations with incident diabetes and related pathophysiology are warranted.

Mechanisms of resiliency against depression following the Deepwater Horizon Oil Spill.

Prior studies of oil spills have reported adverse impacts on mental health, but have not examined some potentially important moderators. In this cross-sectional analysis of n=38,361 responses to the 2010-2011 Gulf States Population Survey, we assessed the association of direct oil contact with depression severity following the Deepwater Horizon oil spill, and modification by self-mastery, emotional support, and cleanup participation using Tobit regression models accounting for the complex survey design. Oil contact was associated with increased depression severity. Among respondents with oil contact, depression was more severe for those reporting lower self-mastery. However, respondents with oil contact had lower depression severity if they participated in cleanup efforts, compared to exposed individuals who did not participate. This potential protective effect was larger for respondents with lower self-mastery. Our results are consistent with the notion that participation in recovery efforts may reduce depressive symptoms following oil spills among impacted individuals.

A cluster-randomized crossover trial of organic diet impact on biomarkers of exposure to pesticides and biomarkers of oxidative stress/inflammation in primary school children.

Despite suggestive observational epidemiology and laboratory studies, there is limited experimental evidence regarding the effect of organic diet on human health. A cluster-randomized 40-day-organic (vs. 40-day-conventional) crossover trial was conducted among children (11-12 years old) from six schools in Cyprus. One restaurant provided all organic meals, and adherence to the organic diet intervention was measured by parent-provided diet questionnaire/diary data. Biomarkers of pyrethroid and neonicotinoid pesticide exposures were measured using tandem mass spectrometry, and oxidative stress/inflammation (OSI) biomarkers using immunoassays or spectrophotometry. Associations were assessed using mixed-effect regression models including interactions of treatment with time. Seventy-two percent of neonicotinoid biomarkers were non-detectable and modeled as binary (whether detectable). In post-hoc analysis, we considered the outcome of age-and-sex-standardized BMI. Multiple comparisons were handled using Benjamini-Hochberg correction for 58 regression parameters. Outcome data were available for 149 children. Children had lower pesticide exposures during the organic period (pyrethroid geometric mean ratio, GMR = 0.297; [95% confidence interval (95% CI): 0.237, 0.373], Q-value<0.05); odds for detection of neonicotinoids (OR = 0.651; [95% CI: 0.463, 0.917), Q-value<0.05); and decreased OSI biomarker 8-OHdG (GMR = 0.888; [95% CI: 0.808, 0.976], Q-value<0.05). An initial increase was followed by a countervailing decrease over time in the organic period for OSI biomarkers 8-iso-PGF2a and MDA. BMI z-scores were lower at the end of the organic period (ß = -0.131; [95% CI: 0.179, -0.920], Q-value<0.05). Energy intake during the conventional period was reported to be higher than the recommended reference levels. The organic diet intervention reduced children's exposure to pyrethroid and neonicotinoid pesticides and, over time lowered biomarkers of oxidative stress/inflammation (8-iso-PGF2a, 8-OHdG and MDA). The several-week organic diet intervention also reduced children's age-and-sex-standardized BMI z-scores, but causal inferences regarding organic diet's physiological benefits are limited by the confounding of the organic diet intervention with caloric intake reduction and possible lifestyle changes during the trial. Trial registration: This trial is registered with ClinicalTrials.gov, number: NCT02998203.

Groundwater Chemistry and Blood Pressure: A Cross-Sectional Study in Bangladesh.

Background: We assessed the association of groundwater chemicals with systolic blood pressure (SBP) and diastolic blood pressure (DBP). Methods: Blood pressure data for ≥35-year-olds were from the Bangladesh Demographic and Health Survey in 2011. Groundwater chemicals in 3534 well water samples from Bangladesh were measured by the British Geological Survey (BGS) in 1998-1999. Participants who reported groundwater as their primary source of drinking water were assigned chemical measures from the nearest BGS well. Survey-adjusted linear regression methods were used to assess the association of each groundwater chemical with the log-transformed blood pressure of the participants. Models were adjusted for age, sex, body mass index, smoking status, geographical region, household wealth, rural or urban residence, and educational attainment, and further adjusted for all other groundwater chemicals. Results: One standard deviation (SD) increase in groundwater magnesium was associated with a 0.992 (95% confidence interval (CI): 0.986, 0.998) geometric mean ratio (GMR) of SBP and a 0.991 (95% CI: 0.985, 0.996) GMR of DBP when adjusted for covariates except groundwater chemicals. When additionally adjusted for groundwater chemicals, one SD increase in groundwater magnesium was associated with a 0.984 (95% CI: 0.972, 0.997) GMR of SBP and a 0.990 (95% CI: 0.979, 1.000) GMR of DBP. However, associations were attenuated following Bonferroni-correction for multiple chemical comparisons in the full-adjusted model. Groundwater concentrations of calcium, potassium, silicon, sulfate, barium, zinc, manganese, and iron were not associated with SBP or DBP in the full-adjusted models. Conclusions: Groundwater magnesium had a weak association with lower SBP and DBP of the participants.

Drinking Water Salinity, Urinary Macro-Mineral Excretions, and Blood Pressure in the Southwest Coastal Population of Bangladesh.

Background Sodium (Na+) in saline water may increase blood pressure ( BP ), but potassium (K+), calcium (Ca2+), and magnesium (Mg2+) may lower BP . We assessed the association between drinking water salinity and population BP . Methods and Results We pooled 6487 BP measurements from 2 cohorts in coastal Bangladesh. We used multilevel linear models to estimate BP differences across water salinity categories: fresh water (electrical conductivity, <0.7 mS/cm), mild salinity (electrical conductivity ≥0.7 and <2 mS/cm), and moderate salinity (electrical conductivity ≥2 and <10 mS/cm). We assessed whether salinity categories were associated with hypertension using multilevel multinomial logistic models. Models included participant-, household-, and community-level random intercepts. Models were adjusted for age, sex, body mass index ( BMI ), physical activity, smoking, household wealth, alcohol consumption, sleep hours, religion, and salt consumption. We evaluated the 24-hour urinary minerals across salinity categories, and the associations between urinary minerals and BP using multilevel linear models. Compared with fresh water drinkers, mild-salinity water drinkers had lower mean systolic BP (-1.55 [95% CI : -3.22-0.12] mm Hg) and lower mean diastolic BP (-1.26 [95% CI : -2.21--0.32] mm Hg) adjusted models. The adjusted odds ratio among mild-salinity water drinkers for stage 1 hypertension was 0.60 (95% CI : 0.43-0.84) and for stage 2 hypertension was 0.56 (95% CI : 0.46-0.89). Mild-salinity water drinkers had high urinary Ca2+, and Mg2+, and both urinary Ca2+ and Mg2+ were associated with lower BP. Conclusions Drinking mild-salinity water was associated with lower BP , which can be explained by higher intake of Ca2+ and Mg2+ through saline water.

Determinants of oil-spill cleanup participation following the Deepwater Horizon oil spill.

BACKGROUND: On April 20, 2010, the Deepwater Horizon oil rig exploded, spilling over 4.9 million barrels of oil in the Gulf of Mexico over an 87-day period and developing into a long-term environmental disaster that affected people living in Gulf Coast states. Engagement of community members in recovery efforts is important for mitigating adverse effects of disasters and accelerating the rebuilding process for impacted communities; however, few studies have explored factors that determine participation in oil spill cleanups. METHODS: We analyzed data from the Gulf States Population Survey (GSPS) to study the determinants of participating in the Deepwater Horizon Oil Spill cleanup. The GSPS was a random-digit dialing survey conducted on 38,361 adults in counties and parishes in Alabama, Florida, Louisiana, and Mississippi impacted by the oil spill. Using survey estimation to account for the complex survey design, we estimated the probability of cleanup participation and used logistic regression to examine the association between sociodemographic factors and cleanup participation. RESULTS: Approximately 4.7% of residents in affected Gulf communities participated in the cleanup. Most participants were young, men, non-Hispanic white, and employed. Living in an affected coastal county was associated with higher odds of participation (unadjusted odds ratio [OR]: 1.69; 95% confidence interval [CI]: 1.28-2.24), as was having excellent or very good physical health (OR: 2.05; 95% CI: 1.11-3.81). Older persons were less likely to participate in the cleanup (OR for 65+ age group vs. 18-24 age group: 0.14; 95% CI: 0.05-0.36). CONCLUSIONS: Understanding the demographics of cleanup participants may help inform civilian recruitment for future oil spill responses.

Arsenic-gene interactions and beta-cell function in the Strong Heart Family Study.

We explored arsenic-gene interactions influencing pancreatic beta-cell activity in the Strong Heart Family Study (SHFS). We considered 42 variants selected for associations with either beta-cell function (31 variants) or arsenic metabolism (11 variants) in the SHFS. Beta-cell function was calculated as homeostatic model - beta corrected for insulin resistance (cHOMA-B) by regressing homeostatic model - insulin resistance (HOMA-IR) on HOMA-B and adding mean HOMA-B. Arsenic exposure was dichotomized at the median of the sum of creatinine-corrected inorganic and organic arsenic species measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS). Additive GxE models for cHOMA-B were adjusted for age and ancestry, and accounted for family relationships. Models were stratified by center (Arizona, Oklahoma, North Dakota and South Dakota) and meta-analyzed. The two interactions between higher vs. lower arsenic and SNPs for cHOMA-B that were nominally significant at P < 0.05 were with rs10738708 (SNP overall effect -3.91, P = 0.56; interaction effect with arsenic -31.14, P = 0.02) and rs4607517 (SNP overall effect +16.61, P = 0.03; interaction effect with arsenic +27.02, P = 0.03). The corresponding genes GCK and TUSC1 suggest oxidative stress and apoptosis as possible mechanisms for arsenic impacts on beta-cell function. No interactions were Bonferroni-significant (1.16 × 10-3). Our findings are suggestive of oligogenic moderation of arsenic impacts on pancreatic ß-cell endocrine function, but were not Bonferroni-significant.

SLCO1B1 variants and urine arsenic metabolites in the Strong Heart Family Study.

Arsenic species patterns in urine are associated with risk for cancer and cardiovascular diseases. The organic anion transporter coded by the gene SLCO1B1 may transport arsenic species, but its association with arsenic metabolites in human urine has not yet been studied. The objective of this study is to evaluate associations of urine arsenic metabolites with variants in the candidate gene SLCO1B1 in adults from the Strong Heart Family Study. We estimated associations between % arsenic species biomarker traits and 5 single-nucleotide polymorphisms (SNPs) in the SLCO1B1 gene in 157 participants, assuming additive genetics. Linear regression models for each SNP accounted for kinships and were adjusted for sex, body mass index, and study center. The minor allele of rs1564370 was associated with lower %MMA (p = .0003) and higher %DMA (p = .0002), accounting for 8% of the variance for %MMA and 9% for %DMA. The rs1564370 minor allele homozygote frequency was 17% and the heterozygote frequency was 43%. The minor allele of rs2291075 was associated with lower %MMA (p = .0006) and higher %DMA (p = .0014), accounting for 7% of the variance for %MMA and 5% for %DMA. The frequency of rs2291075 minor allele homozygotes was 1% and of heterozygotes was 15%. Common variants in SLCO1B1 were associated with differences in arsenic metabolites in a preliminary candidate gene study. Replication of this finding in other populations and analyses with respect to disease outcomes are needed to determine whether this novel candidate gene is important for arsenic-associated disease risks.

Heritability and preliminary genome-wide linkage analysis of arsenic metabolites in urine.

BACKGROUND: Arsenic (III) methyltransferase (AS3MT) has been related to urine arsenic metabolites in association studies. Other genes might also play roles in arsenic metabolism and excretion. OBJECTIVE: We evaluated genetic determinants of urine arsenic metabolites in American Indian adults from the Strong Heart Study (SHS). METHODS: We evaluated heritability of urine arsenic metabolites [percent inorganic arsenic (%iAs), percent monomethylarsonate (%MMA), and percent dimethylarsinate (%DMA)] in 2,907 SHS participants with urine arsenic measurements and at least one relative within the cohort. We conducted a preliminary linkage analysis in a subset of 487 participants with available genotypes on approximately 400 short tandem repeat markers using a general pedigree variance component approach for localizing quantitative trait loci (QTL). RESULTS: The medians (interquartile ranges) for %iAs, %MMA, and %DMA were 7.7% (5.4-10.7%), 13.6% (10.5-17.1%), and 78.4% (72.5-83.1%), respectively. The estimated heritability was 53% for %iAs, 50% for %MMA, and 59% for %DMA. After adjustment for sex, age, smoking, body mass index, alcohol consumption, region, and total urine arsenic concentrations, LOD [logarithm (to the base of 10) of the odds] scores indicated suggestive evidence for genetic linkage with QTLs influencing urine arsenic metabolites on chromosomes 5 (LOD = 2.03 for %iAs), 9 (LOD = 2.05 for %iAs and 2.10 for %MMA), and 11 (LOD = 1.94 for %iAs). A peak for %DMA on chromosome 10 within 2 Mb of AS3MT had an LOD of 1.80. CONCLUSIONS: This population-based family study in American Indian communities supports a genetic contribution to variation in the distribution of arsenic metabolites in urine and, potentially, the involvement of genes other than AS3MT.