A57-17 Mitochondrial DNA Copy Number: A Marker of Exposome-Related Biological Response in World Trade Center Exposed Firefighters

Background

Mitochondrial DNA copy number(mtDNAcn) may serve as a key biomarker for mitochondrial health, cellular energy and oxidative capacity. High mtDNAcn has been associated with both negative (oxidative stress) and positive health effects, whereas low mtDNAcn has been linked to aging, mitochondrial dysfunction, and end-organ dysfunction. The association of mtDNAcn in World Trade Center (WTC) exposure is unknown, and its relevance to WTC-lung injury is under active investigation.

Methods

WTC-exposed firefighters with lung injury (Forced Expiratory Volume in one second (FEV1) < lower limit of normal; N = 63 enrolled in our nutritional intervention) had salivary samples (ORAgene-Discover; OGR-600) collected and assayed by whole genome sequencing. mtDNAcn was estimated by fraction of mitochondrial to autosomal read coverage (NYGenome). Database management and statistical analyses were conducted using SPSS.

Results

Demographics. Participants had a mean (SD) age of 37.5 years (6.8) at 9/11 and 23.1(8.5) years of service. Most participants were non-Hispanic White (95.2%), reported exposure on 9/11 (79.4%), and had a mean duration of 4.27(2.70) months spent at the WTC-site. Mean mtDNAcn was 122.01 (45.39); participants were categorized as high (≥mean, N = 28) or low (<mean, N = 35) mtDNAcn.

mtDNAcn. Ever-smokers (n = 19) had significantly higher mean mtDNAcn compared with never smokers(n = 44), 146.97 (58.63) vs.111.24 (33.74); p = 0.021. Higher alcohol intake (% total calories) was also significantly associated with higher mtDNAcn; 6.66 (5.90) vs. 3.75 (4.12); p=0.030. Firefighters reporting >7% of total caloric intake from monounsaturated fat (n = 7) also had significantly lower mean mtDNAcn compared with those reporting ≤7% (n = 13); 107.91 (24.29) vs. 105.68 (44.83); p=0.023. Higher mtDNAcn was associated with high total fat intake, specifically saturated fat; 15.23% (5.19) vs. 12.07% (2.54); p=0.037. Lower mtDNAcn was also associated with higher forced vital capacity (FVC) [3.64L (0.50) vs. 3.96L (0.49)]; p=0.016), and higher percentage predicted FVC [76.10 (9.95) vs. 82.26 (12.05); p=0.032]. Higher mtDNAcn was also associated with greater improvement in lung function after dietary intervention, including an increase in FEV₁ [0.31L (0.60) vs. -0.02 (0.38); p=0.008], percent predicted FEV₁ [7.81 (15.03) vs. 0.43 (10.07); p=0.024], and FVC [0.32L (0.55) vs.-0.005 (0.48); p=0.015].

Conclusion

In WTC-exposed firefighters with lung injury, mtDNAcn was positively associated with smoking history, fat intake, and worse baseline lung function. Interestingly, high mtDNAcn was also associated with improved lung function in subjects of our nutritional randomized clinical trial. These findings suggest that mtDNAcn may reflect adaptive mitochondrial responses to environmental exposure and pulmonary injury, warranting further investigation.

This abstract is funded by: CDC