Effects of Gene‐Environment Interactions on Endothelial Function in Adolescents: GSTM1 and GSTT1 Polymorphisms and Tobacco Smoke Exposure

Abstract

IntroductionSecond‐hand smoke (SHS) exposure is a significant risk factor for cardiovascular disease (CVD) and related CV complications. SHS exposure increases arterial endothelial damage and has been associated with impaired flow‐mediated vasodilation (FMD), an ultrasonic assessment of endothelial function. There are established ethnic and sex‐related CVD health disparities attributable to SHS exposure among African Americans (AAs). In disease‐free adolescents and adults, AAs also have earlier manifestations of vascular damage including impaired FMD. Furthermore, polymorphisms in glutathione S‐transferase genes GSTM1 and GSTT1 result in the absence of enzyme activity necessary to detoxify several toxins in tobacco smoke. There is a lack of research on the impact of these GST null genotypes on endothelial function, especially within the context of smoke exposure (exposure alone or actual smoker) among normotensive disease‐free adolescents. Also, we are unaware of other studies that have examined these gene‐environment interactions with adolescents who all have an established biological family history of CVD disease (i.e., hypertension and or early myocardial infarction < 55 yrs. of age in at least one parent or grandparent).PurposeTo investigate the potential gene‐environment interactions (GSTM1, GSTT1) and SHS exposure and the moderating effects of ethnicity/race on the pre‐clinical CVD risk factor (i.e. FMD) in an adolescent at‐risk cohort based on family history.MethodsSubjects were 262 normotensive adolescents aged 16–22 yrs., with nearly equal distribution of Caucasians and AAs. SHS exposure was measured by plasma cotinine using liquid chromatography with mass‐spectrometric detection and FMD of the left superficial femoral artery was determined using established procedures. To examine the effect of race, SHS and genotype (i.e., GSTT1 or GSTM1) on FMD, analysis of covariance was used.ResultsCaucasians had higher mean plasma cotinine concentrations compared with AAs (42.2 and 24.6 ng/ml, respectively), and males had higher concentrations than females (73.78 and 31.88 ng/ml, respectively). A significant three‐factor interaction was found between SHS exposure and presence of GSTM1 and GSTT1 (p = 0.016 and 0.0304, respectively) after adjusting for pre‐occlusion arterial diameter. Among all participants, AAs with the GSTM1‐1 genotype and who were also smokers exhibited the poorest %FMD compared to all other subgroups (Adjusted Mean = 0.30; SE 2.28).ConclusionHigher SHS exposure may be particularly harmful based on gene‐environment interactions in African American youth and especially in those who are already at high‐risk of developing CVD based on a positive family history. Although further research is needed, the association between GSTM1‐1 and lower %FMD in AAs may be related to early endothelial dysfunction, which is an independent predictor of CVD risk and events.Support or Funding InformationNIH/National Institute of Nursing Research 03/01/06‐2/28/08R15NR008871; PI: MSTingenThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.