An association study of arsenic exposure, inflammation, oxidative stress and the risk of developing cardiovascular diseases

Arsenic (As) is abundant in the earth’s crust and can be released to groundwater under certain conditions. Several studies using animal models reported that As exposure may increase inflammation and oxidative stress. Abundant evidence showed that inflammation and oxidative stress are related to the developing of cardiovascular diseases (CVDs). Previously, several studies reported that inorganic As in drinking water was associated with the risk of cardiovascular mortality, ischemic heart disease, peripheral vascular disease, atherosclerosis, and cerebral infarction. However, the effects of exposure to lower concentrations of As on these cardiovascular related diseases and genetic contribution to CVD from inflammation and oxidative stress under As exposure are still unclear. About 4500 residents who have been participated in the Lanyang cohort during 1991-1994 will be invited to this project for updating their data in the disease status. The information of life style and biological risk factors will be collected from all study subjects through a structured questionnaire during home-visit interview. The status of CVD will be confirmed through health screening in the local hospitals or data linkage to the NHI databank. Genotyping of inflammatory related genes (PPARα, PPARβ, NF-kB, VCAM1, CCR2, RANTES, and TLR4) and oxidative stress related genes (iNOS, eNOS, p66Shc, RAGE, NQO1, and Nrf2) will be determined by the methods of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or real-time polymerase chain reaction (RT-PCR). In this project, we aim to clarify the relationship between the risk of CVDs and As exposure at lower levels and to evaluate the gene-gene and gene-environment interactions between inflammatory-related genes, oxidative stress-related genes and As exposure on the risk of CVDs.