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Urinary metals and leukocyte telomere length in American Indian communities: The Strong Heart and the Strong Heart Family Study.

ABSTRACT: INTRODUCTION:While several mechanisms may explain metal-related health effects, the exact cellular processes are not fully understood. We evaluated the association between leukocyte telomere length (LTL) and urine arsenic (?As), cadmium (Cd) and tungsten (W) exposure in the Strong Heart Study (SHS, N?=?1702) and in the Strong Heart Family Study (SHFS, N?=?1793). METHODS:Urine metal concentrations were measured using ICP-MS. Arsenic exposure was assessed as the sum of inorganic arsenic, monomethylarsonate and dimethylarsinate levels (?As). LTL was measured by quantitative polymerase chain reaction. RESULTS:In the SHS, median levels were 1.09 for LTL, and 8.8, 1.01 and 0.11??g/g creatinine for ?As, Cd, and W, respectively. In the SHFS, median levels were 1.01 for LTL, and 4.3, 0.44, and 0.10??g/g creatinine. Among SHS participants, increased urine ?As, Cd, and W was associated with shorter LTL. The adjusted geometric mean ratio (95% confidence interval) of LTL per an increase equal to the difference between the percentiles 90th and 10th in metal distributions was 0.85 (0.79, 0.92) for ?As, 0.91 (0.84, 1.00) for Cd and 0.93 (0.88, 0.98) for W. We observed no significant associations among SHFS participants. The findings also suggest that the association between arsenic and LTL might be differential depending on the exposure levels or age. CONCLUSIONS:Additional research is needed to confirm the association between metal exposures and telomere length.

SUBMITTER: Grau-Perez M

PROVIDER: S-EPMC6363843 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Urinary metals and leukocyte telomere length in American Indian communities: The Strong Heart and the Strong Heart Family Study.

Grau-Perez Maria M Zhao Jinying J Pierce Brandon B Francesconi Kevin A KA Goessler Walter W Zhu Yun Y An Qiang Q Umans Jason J Best Lyle L Cole Shelley A SA Navas-Acien Ana A Tellez-Plaza Maria M

Environmental pollution (Barking, Essex : 1987) 20181205

<h4>Introduction</h4>While several mechanisms may explain metal-related health effects, the exact cellular processes are not fully understood. We evaluated the association between leukocyte telomere length (LTL) and urine arsenic (ΣAs), cadmium (Cd) and tungsten (W) exposure in the Strong Heart Study (SHS, N = 1702) and in the Strong Heart Family Study (SHFS, N = 1793).<h4>Methods</h4>Urine metal concentrations were measured using ICP-MS. Arsenic exposure was assessed as the sum of inorganic ars ...[more]

PMID: 30557805

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Project description:Essentials Plasminogen activator inhibitor-1 (PAI-1) advanced cellular senescence in experiment studies. No population study exists on the association between PAI-1 and biological aging in American Indians. We found cross-sectional and longitudinal associations between higher PAI-1 and shorter telomere length. Our findings suggest a pathway linking PAI-1 with biological aging beyond metabolic factors. SUMMARY:Background Plasminogen activator inhibitor-1 (PAI-1) promotes cellular aging both in vitro and in vivo. Telomere length is a marker of biological aging. Objectives To examine the cross-sectional and longitudinal associations between plasma PAI-1 and leukocyte telomere length in a large-scale epidemiological study of American Indians. Methods We measured leukocyte telomere length (LTL) and plasma PAI-1 in 2560 American Indians who were free of overt cardiovascular disease (CVD) and participated in the Strong Heart Family Study (SHFS) clinical examination in 2001-2003. LTL and PAI-1 were repeatedly measured in 475 participants who attended SHFS clinical visits in both 2001-2003 and 1998-1999. A generalized estimating equation model was used to examine the cross-sectional and longitudinal associations between PAI-1 and LTL, adjusting for known risk factors. Results A higher level of plasma PAI-1 was negatively associated with shorter age-adjusted LTL (? = -0.023; 95% CI, -0.034 to -0.013). This association was attenuated (? = -0.015; 95% CI, -0.029 to -0.002) after adjustments for demographics, study site, lifestyle (smoking, drinking and physical activity) and metabolic factors (obesity, blood pressure, fasting glucose, insulin, lipids and kidney function). Further adjustment for hsCRP did not change this association (? = -0.015; 95% CI, -0.029 to -0.001). Longitudinal analysis revealed that change in plasma PAI-1 was also inversely associated with change in LTL after adjusting for demographics, follow-up years, lifestyle factors, changes in metabolic factors, baseline levels of PAI-1 and LTL (? = -0.0005; 95% CI, -0.0009 to -0.0001). Conclusions A higher level of plasma PAI-1 was associated with shorter LTL in American Indians. This finding may suggest a potential role of PAI-1 in biological aging among American Indians.

Project description:Metabolism of inorganic arsenic (iAs) is subject to inter-individual variability, which is explained partly by genetic determinants.We investigated the association of genetic variants with arsenic species and principal components of arsenic species in the Strong Heart Family Study (SHFS).We examined variants previously associated with cardiometabolic traits (~ 200,000 from Illumina Cardio MetaboChip) or arsenic metabolism and toxicity (670) among 2,428 American Indian participants in the SHFS. Urine arsenic species were measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS), and percent arsenic species [iAs, monomethylarsonate (MMA), and dimethylarsinate (DMA), divided by their sum × 100] were logit transformed. We created two orthogonal principal components that summarized iAs, MMA, and DMA and were also phenotypes for genetic analyses. Linear regression was performed for each phenotype, dependent on allele dosage of the variant. Models accounted for familial relatedness and were adjusted for age, sex, total arsenic levels, and population stratification. Single nucleotide polymorphism (SNP) associations were stratified by study site and were meta-analyzed. Bonferroni correction was used to account for multiple testing.Variants at 10q24 were statistically significant for all percent arsenic species and principal components of arsenic species. The index SNP for iAs%, MMA%, and DMA% (rs12768205) and for the principal components (rs3740394, rs3740393) were located near AS3MT, whose gene product catalyzes methylation of iAs to MMA and DMA. Among the candidate arsenic variant associations, functional SNPs in AS3MT and 10q24 were most significant (p < 9.33 × 10-5).This hypothesis-driven association study supports the role of common variants in arsenic metabolism, particularly AS3MT and 10q24. Citation: Balakrishnan P, Vaidya D, Franceschini N, Voruganti VS, Gribble MO, Haack K, Laston S, Umans JG, Francesconi KA, Goessler W, North KE, Lee E, Yracheta J, Best LG, MacCluer JW, Kent J Jr., Cole SA, Navas-Acien A. 2017. Association of cardiometabolic genes with arsenic metabolism biomarkers in American Indian communities: the Strong Heart Family Study (SHFS). Environ Health Perspect 125:15-22;?http://dx.doi.org/10.1289/EHP251.

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Urinary metals and leukocyte telomere length in American Indian communities: The Strong Heart and the Strong Heart Family Study.

Publications

Urinary metals and leukocyte telomere length in American Indian communities: The Strong Heart and the Strong Heart Family Study.

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