Particulate matter exposure during pregnancy increases risk of childhood asthma: modified by gender and NRF2 genotype

Hyo-Bin Kim,¹ Hyeyeun Lim,² Sangrok Kim,² So-Yeon Lee,² Hwan-Cheol Kim,³ Mi-Jin Kang,² Minjee Park,²
Sungsu Jung,⁴ Jisun Yoon,⁵ Hyun-Ju Cho,⁶ Song-I Yang,⁷ Soo-Jong Hong²

Affiliations:
¹ Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, Korea
² Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
³ Department of Occupational and Environmental Medicine, Inha University School of Medicine, Incheon, Korea
⁴ Department of Pediatrics, Pusan National University Yangsan Hospital, Yangsan, Korea
⁵ Department of Pediatrics, Chung-Ang University Gwang-Myeong Hospital, Chung-Ang University College of Medicine, Gwang-Myeong, Korea
⁶ Department of Pediatrics, International St. Mary’s Hospital, Catholic Kwandong University Hospital, Incheon, Korea
⁷ Department of Pediatrics, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea

Abstract

Background: Exposure to particulate matter (PM) has been known to develop asthma in children and the oxidative stress-related mechanisms are suggested. For the development of asthma, not only the exposure dose but also the critical window and the risk modifying factors should be evaluated.
Objective: We investigated whether prenatal exposure to PM₁₀ increases the risk of childhood asthma and evaluated the modifying factors, such as gender and reactive oxidative stress-related gene.
Methods: A general population-based birth cohort, the Panel Study of Korean Children (PSKC), including 1572 mother-baby dyads was analyzed. Children were defined to have asthma at age 7 when a parent reported physician-diagnosed asthma. Exposure to PM₁₀ during pregnancy was estimated by land-use regression models based on national monitoring system. TaqMan method was used for genotyping nuclear factor, erythroid 2-related factor, NRF2 (rs6726395). A logistic Bayesian distributed lag interaction model (BDLIM) was used to evaluate the associations between prenatal PM₁₀ exposure and childhood asthma by gender and NRF2.
Results: Exposure to PM₁₀ during pregnancy was associated with the development of asthma (aOR 1.03, 95% CI 1.00-1.06). Stratifying by gender and NRF2 genotype, exposure to PM₁₀ during 26-28 weeks gestation increased the risk of childhood asthma, especially in boys with NRF2 GG genotype.
Conclusion: A critical window for PM₁₀ exposure on the development of childhood asthma was during 26-28 weeks of gestation, and this was modified by gender and NRF2 genotype.
Key words: asthma, gender, gene, NRF2, particulate matter, pregnancy