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)
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