TY - JOUR
T1 - Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima-media thickness in Bangladesh
AU - Wu, Fen
AU - Jasmine, Farzana
AU - Kibriya, Muhammad G.
AU - Liu, Mengling
AU - Cheng, Xin
AU - Parvez, Faruque
AU - Paul-Brutus, Rachelle
AU - Islam, Tariqul
AU - Paul, Rina Rani
AU - Sarwar, Golam
AU - Ahmed, Alauddin
AU - Jiang, Jieying
AU - Islam, Tariqul
AU - Slavkovich, Vesna
AU - Rundek, Tatjana
AU - Demmer, Ryan T.
AU - Desvarieux, Moise
AU - Ahsan, Habibul
AU - Chen, Yu
N1 - Funding Information:
This work is supported by the National Institutes of Health grants: R01ES017541 , R01CA107431 , P42ES010349 , P30ES000260 , R01CA107431 , and K24 NS 062737 (TR).
PY - 2014/5/1
Y1 - 2014/5/1
N2 - Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima-media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥. 40.4. μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9. μm (95% CI. =. 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β. =. -. 5.1. μm, 95% CI. =. -. 31.6, 21.3) or arsenic exposure alone (β. =. 7.2. μm, 95% CI. =. -. 3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings.
AB - Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima-media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥. 40.4. μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9. μm (95% CI. =. 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β. =. -. 5.1. μm, 95% CI. =. -. 31.6, 21.3) or arsenic exposure alone (β. =. 7.2. μm, 95% CI. =. -. 3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings.
KW - Arsenic
KW - Bangladesh
KW - Cardiovascular diseases
KW - Carotid artery intima-media thickness
KW - Drinking water
KW - Single nucleotide polymorphism
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UR - http://www.scopus.com/inward/citedby.url?scp=84897505993&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2014.02.014
DO - 10.1016/j.taap.2014.02.014
M3 - Article
C2 - 24593923
AN - SCOPUS:84897505993
SN - 0041-008X
VL - 276
SP - 195
EP - 203
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 3
ER -
