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Association of exposure to prenatal perfluoroalkyl substances and estrogen receptor 1 polymorphisms with the second to fourth digit ratio in school-aged children : The Hokkaido study

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Title: Association of exposure to prenatal perfluoroalkyl substances and estrogen receptor 1 polymorphisms with the second to fourth digit ratio in school-aged children : The Hokkaido study
Authors: Nishimura, Yoko Browse this author
Moriya, Kimihiko Browse this author
Kobayashi, Sumitaka Browse this author →KAKEN DB
Ikeda-Araki, Atsuko Browse this author
Sata, Fumihiro Browse this author
Mitsui, Takahiko Browse this author
Itoh, Sachiko Browse this author
Miyashita, Chihiro Browse this author
Cho, Kazutoshi Browse this author
Kon, Masafumi Browse this author
Nakamura, Michiko Browse this author
Kitta, Takeya Browse this author
Murai, Sachiyo Browse this author
Kishi, Reiko Browse this author →KAKEN DB
Shinohara, Nobuo Browse this author →KAKEN DB
Keywords: Per- and polyfluoroalkyl substances
ESR1 polymorphism & nbsp
Hand digit ratio
Birth cohort
Gene environment interaction
Issue Date: Apr-2022
Publisher: Elsevier
Journal Title: Reproductive toxicology
Volume: 109
Start Page: 10
End Page: 18
Publisher DOI: 10.1016/j.reprotox.2022.02.002
Abstract: Per-and Polyfluoroalkyl substances (PFAS) have endocrine-disrupting effects. The ratio of the lengths of the second and fourth digits (2D:4D) is a noninvasive retrospective index of prenatal exposure to sex hormones, and estrogen receptor 1 (ESR1) polymorphisms may contribute to 2D:4D determination. We investigated whether ESR1 polymorphisms modify the effects of prenatal PFAS exposure on 2D:4D. Participants (n = 1024) with complete data in a prospective birth cohort study (the Hokkaido Study) were included, and maternal plasma in the third trimester was used to examine PFAS concentrations. 2D:4D was determined from photocopies of palms of children using Vernier calipers. ESR1 polymorphisms (rs2234693, rs9340799, and rs2077647) were genotyped by TaqMan polymerase chain reaction. PFAS and 2D:4D association with ESR1 polymorphisms was assessed by multiple linear regression adjusted for potential confounding factors. A 10-fold increase in maternal perfluorooctanoic acid (PFOA) concentration was associated with a 1.54% [95% confidence interval (CI): 0.40, 2.68] increase in mean 2D:4D in children with an AA genotype at rs9340799 and a 2.24% (95% CI: 0.57, 3.92) increase in children with an AA genotype at rs2077647. A 10-fold increase in perfluorododecanoic acid (PFDoDA) was associated with a significant increase in 2D:4D in children with the AA genotype [rs9340799, 1.18% (95% CI: 0.02, 2.34); and rs2077647, 1.67% (95% CI: 0.05, 3.28)]. These associations were apparent among males. A significant gene-environment interaction between PFOA or PFDoDA and ESR1 polymorphism was detected. These findings suggest that ESR1 polymorphisms modify the effects of prenatal exposure to PFAS on sex differentiation.
Rights: © 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
http://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article (author version)
URI: http://hdl.handle.net/2115/88786
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 篠原 信雄

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