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Gene-arsenic interaction in longitudinal changes of blood pressure: Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh.

ABSTRACT: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide and mounting evidence indicates that toxicant exposures can profoundly impact on CVD risk. Epidemiologic studies have suggested that arsenic (As) exposure is positively related to increases in blood pressure (BP), a primary CVD risk factor. However, evidence of whether genetic susceptibility can modify the association between As and BP is lacking. In this study, we used mixed effect models adjusted for potential confounders to examine the interaction between As exposure from well water and potential genetic modifiers on longitudinal change in BP over approximately 7years of follow-up in 1137 subjects selected from the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in Bangladesh. Genotyping was conducted for 235 SNPs in 18 genes related to As metabolism, oxidative stress and endothelial function. We observed interactions between 44 SNPs with well water As for one or more BP outcome measures (systolic, diastolic, or pulse pressure (PP)) over the course of follow-up. The interaction between CYBA rs3794624 and well water As on annual PP remained statistically significant after correction for multiple comparisons (FDR-adjusted p for interaction=0.05). Among individuals with the rs3794624 variant genotype, well water As was associated with a 2.23mmHg (95% CI: 1.14-3.32) greater annual increase in PP, while among those with the wild type, well water As was associated with a 0.13mmHg (95% CI: 0.02-0.23) greater annual increase in PP. Our results suggest that genetic variability may contribute to As-associated increases in BP over time.

SUBMITTER: Farzan SF

PROVIDER: S-EPMC4606937 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Gene-arsenic interaction in longitudinal changes of blood pressure: Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh.

Farzan Shohreh F SF Karagas Margaret R MR Jiang Jieying J Wu Fen F Liu Mengling M Newman Jonathan D JD Jasmine Farzana F Kibriya Muhammad G MG Paul-Brutus Rachelle R Parvez Faruque F Argos Maria M Scannell Bryan Molly M Eunus Mahbub M Ahmed Alauddin A Islam Tariqul T Rakibuz-Zaman Muhammad M Hasan Rabiul R Sarwar Golam G Slavkovich Vesna V Graziano Joseph J Ahsan Habibul H Chen Yu Y

Toxicology and applied pharmacology 20150726 1

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide and mounting evidence indicates that toxicant exposures can profoundly impact on CVD risk. Epidemiologic studies have suggested that arsenic (As) exposure is positively related to increases in blood pressure (BP), a primary CVD risk factor. However, evidence of whether genetic susceptibility can modify the association between As and BP is lacking. In this study, we used mixed effect models adjusted for potenti ...[more]

PMID: 26220686

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Project description:INTRODUCTION:Environmental exposure to toxic metals and metalloids is pervasive and occurs from multiple sources. The Health Effects of Arsenic Longitudinal Study (HEALS) is an ongoing prospective study predominantly focused on understanding health effects associated with arsenic exposure from drinking water. The goal of this project was to measure a suite of elements in urine to better understand potential exposure patterns and to identify common environmental sources of exposure among this semi-rural Bangladeshi population. METHODS:In a random sample of 199 adult HEALS participants (50% female), the concentrations of 15 urinary elements (As, Ba, Cd, Co, Cs, Cu, Mn, Mo, Ni, Pb, Se, Sr, Tl, W, Zn) were assessed by Inductively-Coupled Plasma Mass Spectrometry (ICP-MS) to assess commonalities with sociodemographic characteristics and potential sources of exposure. We used principal component analysis (PCA) with varimax normalized rotations, and hierarchical cluster analysis (CA), using Ward's method with Euclidean distances, to evaluate these relationships. RESULTS:PCA and CA showed similar patterns, suggesting 6 principal components (PC) and 5 clusters: 1)PC: Sr-Ni-Cs/ CA: Sr-Ni-Co; 2) Pb-Tl/Pb-Tl-Se-Cs; 3) As-Mo-W/As-Mo-W; 4) Ba-Mn/Ba-Mn; 5) Cu-Zn/Cu-Zn-Cd; and 6) Cd. There was a strong significant association between the As-Mo-W PC/cluster and water arsenic levels (p?<?0.001) and between the Cd PC and betel nut use (p?=?0.003). The Sr-Ni-Cs PC was not related to any of the socio-demographic characteristics investigated, including smoking status and occupation. The first PC, Sr-Ni-Cs, explained 21% of the variability; the third PC, As-Mo-W, explained 12.5% of the variability; and the sixth PC, Cd, explained 10% of the variability. Day laborers appeared to have the highest exposure. CONCLUSIONS:Groundwater and betel nut use are likely important sources of metal and metalloid exposure in this population. These findings will guide future exposure assessment research in Bangladesh and future epidemiologic research investigating the degree to which metal mixtures play a role in disease development.

Project description:ObjectivesDespite a hypothesised connection of reproductive history with hypertension and mortality, the nature of this association is poorly characterised. We evaluated the association of parity and gravidity with blood pressure, hypertension and all-cause mortality.DesignProspective cohort study.SettingHealth Effects of Arsenic Longitudinal Study cohort in rural Bangladesh.ParticipantsThere were 21 634 Bangladeshi women recruited in 2000-2002, 2006-2008 and 2010-2014 included in the present analysis.MethodsReproductive history was ascertained through an interviewer-administered questionnaire at the baseline visit. Blood pressure was measured by a trained study physician following a standard protocol at the baseline visit. Vital status was ascertained at the biennial follow-up of study participants through June 2017. Linear and logistic regression models estimated the relationship between parity and gravidity with blood pressure and hypertension, respectively. Cox proportional hazards models estimated the relationship with all-cause mortality only among women aged >45 years.ResultsDiastolic blood pressure was lowest in women with parity one (reference) and elevated in nulliparous women (adjusted % change=3.12; 95% CI 1.93 to 4.33) and women with parity >2 (adjusted % change=1.71; 95% CI 1.12 to 2.31). The associations with nulliparity were stronger for women aged >45 years. Similar association patterns were observed with hypertension. Further, in nulliparous women aged >45 years, 265 deaths (6.6%) were ascertained during the follow-up period (median follow-up time=8 years), and we observed suggestive elevated risks of all-cause mortality (adjusted HR 3.83; 95% CI 0.74 to 19.78). The relationships between reproductive history, blood pressure, hypertension and mortality were similar when modelling reproductive history as gravidity rather than parity.ConclusionsFor women in rural Bangladesh, nulliparity and nulligravidity appear to be associated with higher blood pressure and subsequent elevated risk of mortality.

Project description:BackgroundWhile changes in blood pressure (BP) are independently associated with cardiovascular events, less is known about the association between changes in BP and subsequent changes in renal function in adults with an estimated glomerular filtration rate (eGFR) of >60 ml/min/1.73 m2.MethodsThe present study included 3,920 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) study who had ≥2 BP measurements during the first 5 years of MESA and had eGFR measurements at both year 5 and 10. Change in BP was estimated as the annualized slope of BP between year 0 and 5 based on linear mixed models (mean number of measurements = 4.0). Participants were then grouped into 1 of 3 categories based on the distribution of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) change (top 20%, middle 21-79%, bottom 20%). We calculated eGFR from cystatin C (ml/min/1.73 m2), estimated annual change in eGFR (ml/min/1.73 m2/year), and defined rapid kidney function decline as a >30% decrease in eGFR from year 5 to 10. We used multivariable logistic regression adjusting for year 0 demographic and clinical characteristics, including eGFR and BP, to determine associations of BP change with rapid kidney function decline.ResultsMedian age was 59 [interquartile range (IQR): 52, 67] and median eGFR at year 0 was 95.5 (IQR: 81.7, 105.9) ml/min/1.73 m2. Median SBP at year 0 was 111, 121, and 147 mm Hg for increasing, stable, and decreasing SBP change, respectively. Increasing SBP and widening PP change were each associated with higher odds of rapid kidney function decline compared with stable SBP and PP groups, respectively [odds ratio, OR 1.7 (95% confidence interval, CI 1.3, 2.4) for SBP; OR 1.4 (95% CI 1.1, 1.9) for PP]. Decreasing SBP was associated with rapid kidney function decline after adjusting for all covariates except for year 0 BP [OR 1.4 (95% CI 1.0, 1.8)], but this association was no longer statistically significant after adjustment for year 0 BP. There were no significant associations between DBP change and rapid decline in the fully adjusted models. Similar findings were seen with annual change in eGFR.ConclusionsIncreasing SBP and widening PP over time were associated with greater risk for accelerated kidney function decline even at BP levels below established hypertension thresholds.

Dataset Information

Gene-arsenic interaction in longitudinal changes of blood pressure: Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh.

Publications

Gene-arsenic interaction in longitudinal changes of blood pressure: Findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh.

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