Interaction Effects of Long-Term Air Pollution Exposure and Variants in the GSTP1, GSTT1 and GSTCD Genes on Risk of Acute Myocardial Infarction and Hypertension: A Case-Control Study

Abstract

IntroductionExperimental and epidemiological studies have reported associations between air pollution exposure, in particular related to vehicle exhaust, and cardiovascular disease. A potential pathophysiological pathway is pollution-induced pulmonary oxidative stress, with secondary systemic inflammation. Genetic polymorphisms in genes implicated in oxidative stress, such as GSTP1, GSTT1 and GSTCD, may contribute to determining individual susceptibility to air pollution as a promoter of coronary vulnerability.AimsWe aimed to investigate effects of long-term traffic-related air pollution exposure, as well as variants in GSTP1, GSTT1 and GSTCD, on risk of acute myocardial infarction (AMI) and hypertension. In addition, we studied whether air pollution effects were modified by the investigated genetic variants.MethodsGenotype data at 7 single nucleotide polymorphisms (SNPs) in the GSTP1 gene, and one in each of the GSTT1 and GSTCD genes, as well as air pollution exposure estimates, were available for 119 AMI cases and 1310 randomly selected population controls. Population control individuals with systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg or on daily antihypertensive medication were defined as hypertensive (n = 468). Individual air pollution exposure levels were modeled as annual means of NO2 (marker of vehicle exhaust pollutants) using central monitoring data and dispersion models, linking to participants' home addresses.ResultsAir pollution was significantly associated with risk of AMI: OR 1.78 (95%CI 1.04–3.03) per 10 µg/m3 of long-term NO2 exposure. Three GSTP1 SNPs were significantly associated with hypertension. The effect of air pollution on risk of AMI varied by genotype strata, although the suggested interaction was not significant. We saw no obvious interaction between genetic variants in the GST genes and air pollution exposure for hypertension.ConclusionAir pollution exposure entails an increased risk of AMI, and this risk differed over genotype strata for variants in the GSTP1, GSTT1 and GSTCD genes, albeit not statistically-significantly.

Associations of Short-Term and Long-Term Exposure to Ambient Air Pollutants With Hypertension

“…4,5,10,12,[23][24][25][26][27][28][29] We used a standardized table to extract the following information from all of the included articles: authors, publication year, study setting, study population, study duration, study design, short-term or long-term effect, exposure measurement method, data source, number of controls and cases, type of air pollution, exposure mean and range, adjusted odds ratio (OR) and their 95% confidence intervals (CIs), adjusted covariates, and the number of lag days for short-effect if applicable. Eligibility assessments and all of the data extraction were checked and verified by consensus of the 2 investigators.…”

“…Of the 17 included studies, 3 studies defined hypertension as systolic blood pressure ≥140 mm Hg and diastolic blood pressure ≥90 mm Hg 4,24,25 ; 5 studies defined hypertension according to the ICD9 or ICD10 code [6][7][8][9]21 ; 2 studies used self-reported doctor-diagnosed hypertension 5,27 ; and 7 studies used >1 methods to define the hypertension cases 10,12,21,23,26,28,29 ( Tables 1 and 2). …”

“…Four studies assessed the air pollution exposure using complex dispersion models or land use regression models that included various databases, including traffic, meteorology, roadway geometry, vehicle emission, air quality monitoring data, and land use. 5,23,28,29 These models could estimate each subject's exposure level with high accuracy. One study used both data from central air pollution monitoring stations and self-monitoring data 8 ( Tables 1 and 2).…”

“…4,5,10,12,[23][24][25][26][27][28][29] Of these studies, the most common epidemiological designs were cross-sectional (n=5) and cohort studies (n=4). Two other studies were casecontrol designs.…”

Atopic dermatitis: Interaction between genetic variants of GSTP1,TNF,TLR2, and TLR4 and air pollution in early life

“…Specifically, genes belonging to the glutathione S-transferase (GST) family are of particular interest because of their role in cellular protection against oxidative stress, which is a potential pathway for toxic air pollution effects. 12 Recently, evidence has found that children with GST pi 1 (GSTP1) and GST Mu 1 (GSTM1) genotypes may constitute a susceptible population at increased risk of asthma associated with TRAP 13,14 and of childhood AD associated with prenatal smoke exposure. 15 In addition, there is growing evidence that air pollutants activate Toll-like receptor (TLR) signaling, resulting in a pro-inflammatory response in the lung, 16 and a previous study in the PIAMA cohort identified a gene by TRAP interaction for TLR2 and TLR4 variants with respect to asthma.…”