Association of Cardiometabolic Genes with Arsenic Metabolism Biomarkers in American Indian Communities: The Strong Heart Family Study (SHFS)

被引：26

作者：

Balakrishna, Poojitha ^{[1
,2
,3
]}

Vaidya, Dhananjay ^{[2
,4
]}

Franceschini, Nora ^{[5
]}

Voruganti, V. Saroja ^{[6
,7
]}

Gribble, Matthew O. ^{[8
]}

Haack, Karin ^{[9
]}

Laston, Sandra ^{[10
]}

Umans, Jason G. ^{[11
,12
]}

Francesconi, Kevin A. ^{[13
]}

Goessler, Walter ^{[13
]}

North, Karie E. ^{[5
]}

Lee, Elisa ^{[14
]}

Yracheta, Joseph ^{[15
]}

Best, Lyle G. ^{[15
]}

MacCluer, Jean W. ^{[9
]}

Kent, Jack, Jr. ^{[9
]}

Cole, Shelley A. ^{[9
]}

Navas-Acien, Ana ^{[1
,2
,3
,16
]}

机构：

[1] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA

[3] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA

[4] Johns Hopkins Sch Med, Clin & Translat Res, Baltimore, MD USA

[5] Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA

[6] Univ North Carolina Chapel Hill, Dept Nutr, Chapel Hill, NC USA

[7] Univ North Carolina Chapel Hill, UNC Nutr Res Inst, Kannapolis, NC USA

[8] Emory Univ, Dept Environm Hlth, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA

[9] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA

[10] Univ Texas Rio Grande Valley, South Texas Diabet & Obes Inst, Brownsville, TX USA

[11] MedStar Hlth Res Inst, Hyattsville, MD USA

[12] Georgetown & Howard Univ Ctr Clin & Translat Sci, Washington, DC USA

[13] Graz Univ, Inst Chem Analyt Chem, A-8010 Graz, Austria

[14] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA

[15] Missouri Breaks Ind Res Inc, Timber Lake, SD USA

[16] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA

来源：

ENVIRONMENTAL HEALTH PERSPECTIVES | 2017年 / 125卷 / 01期

基金：

美国国家卫生研究院;

关键词：

SKELETAL-MUSCLE; CARDIOVASCULAR-DISEASE; OXIDATIVE STRESS; LINKAGE ANALYSIS; WHOLE-BLOOD; URINE; EXPOSURE; POLYMORPHISMS; HERITABILITY; METHYLATION;

D O I：

10.1289/EHP251

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

BACKGROUND: Metabolism of inorganic arsenic (iAs) is subject to inter-individual variability, which is explained partly by genetic determinants. OBJECTIVES: We investigated the association of genetic variants with arsenic species and principal components of arsenic species in the Strong Heart Family Study (SHFS). METHODS: We examined variants previously associated with cardiometabolic traits (similar to 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 x 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. RESULTS: 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 x 10(-5)). CONCLUSIONS: This hypothesis-driven association study supports the role of common variants in arsenic metabolism, particularly AS3MT and 10q24.

引用

页码：15 / 22

页数：8

共 56 条

[1] Merlin-rapid analysis of dense genetic maps using sparse gene flow trees [J].