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©The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved.
Association of FADS2 polymorphism rs174538 with fatty acid metabolism and disease severity in Japanese patients with Crohn’s disease
Hideyuki Matsuzawa, Zensho Ito, Kan Uchiyama, Yutaro Motoi, Yuichiro Ohtaki, Yuko Iwashita, Shizuka Suzuki, Tatsuya Nakada, Shigeo Koido, Kana Kojima, Kota Murohashi, Masayuki Saruta, Toshifumi Ohkusa, Takahiro Kubota
Hideyuki Matsuzawa, Yutaro Motoi, Kana Kojima, Kota Murohashi, Takahiro Kubota, Faculty of Pharmacy, Department of Biopharmaceutics, Niigata University of Pharmacy and Medical and Life Sciences, Niigata 956-8603, Japan
Zensho Ito, Kan Uchiyama, Yuichiro Ohtaki, Yuko Iwashita, Shizuka Suzuki, Tatsuya Nakada, Shigeo Koido, Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University Kashiwa Hospital, Chiba 277-8567, Japan
Masayuki Saruta, Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan
Toshifumi Ohkusa, Department of Microbiota Research, Juntendo University Graduate School of Medicine, Tokyo 113-0033, Japan
Author contributions: Motoi Y, Kojima K, Murohashi K, and Kubota T conducted a genetic polymorphism study of the FADS2 gene; Ito Z, Uchiyama K, Ohtaki Y, Iwashita Y, Suzuki S, Nakada T, Koido S, Saruta M, and Ohkusa T investigated fatty acid composition and disease activity in patients with Crohn’s disease; Matsuzawa H, Uchiyama K, and Kubota T analyzed the relationships of FADS2 genetic polymorphisms with fatty acid composition and disease activity in patients with Crohn’s disease.
Institutional review board statement: The study was approved by the Clinical Research Ethics Committee of the Jikei University School of Medicine and the Jikei University Kashiwa Hospital (No. 26-363-7869), as well as the Clinical Research Ethics Committee of Niigata University of Pharmacy and Applied Life Sciences (No. H27-005).
Informed consent statement: All subjects provided written informed consent.
Conflict-of-interest statement: There are no conflicts of interest.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Hideyuki Matsuzawa, Doctorate Student, Faculty of Pharmacy, Depart
ment of Biopharmaceutics, Niigata University of Pharmacy and Medical and Life Sciences, 265-1 Higashijima, Akiha-Ku, Niigata 956-8603, Japan.
hideyuki.m.0918@gmail.com
Received: July 31, 2025
Revised: September 2, 2025
Accepted: November 28, 2025
Published online: January 14, 2026
Processing time: 165 Days and 21 Hours
BACKGROUND
Crohn’s disease (CD) is a chronic inflammatory bowel disease with unknown etiology. Inflammatory chemical mediators synthesized from arachidonic acid, an n-6 polyunsaturated fatty acid (PUFA), have been shown to activate CD. Additionally, n-3 PUFAs are metabolized by the same enzyme as n-6 PUFAs and known to inhibit the arachidonic acid cascade. Our previous study noted that the presence of erythrocyte membrane fatty acids is a characteristic finding in Japanese CD patients. It was thus speculated that FADS2 gene polymorphisms, which induce PUFA metabolizing enzymes, are involved in the pathogenesis of CD, though no such relationship was found.
AIM
To investigate the relationship of FADS2 polymorphisms with serum and erythrocyte membrane fatty acid composition ratios, and disease activity.
METHODS
Using previously reported findings regarding FADS2 genetic polymorphisms, the records of 52 CD patients undergoing treatment at Jikei University Kashiwa Hospital were analyzed. Mutations noted were divided into three groups; wild-type (GG), heterozygous mutants (GA), and homozygous (AA), with the activities of delta-6 and delta-5 desaturases compared using redefined d6d index (rd.d6di) and d5d index (d5di). Additionally, comparisons of serum and erythrocyte membranes for fatty acid composition, and also gene polymorphisms and CD activity index (CDAI) were performed.
RESULTS
The presence of the rs174538 mutation in FADS2 resulted in reduction of only rd.d6di in the erythrocyte membrane (P < 0.01). In contrast, that mutation was found to be associated with d5di induced by FADS1 in serum (P = 0.019) as well as the erythrocyte membrane (P < 0.0001), and also with reduction in the fatty acid composition of arachidonic acid in both serum (P < 0.0001) and the erythrocyte membrane (P < 0.01). Regarding disease activity, a positive correlation of CDAI score with rd.d6di in both serum (P < 0.05) and the erythrocyte membrane (P < 0.05) was found only in the rs174538 wild-type group. In contrast, there was no correction between CDAI and d5di in either serum or erythrocyte membrane samples.
CONCLUSION
The rs174538 mutation alters the fatty acid profile through strong linkage to the FADS1 gene. In wild-type individuals, rd.d6di was positively correlated with CDAI, suggesting predictive utility of disease severity.
Core Tip: Erythrocyte membrane fatty acid composition ratios in Japanese Crohn’s disease (CD) patients are distinctive. Analysis was performed to determine effects on FADS2 genetic polymorphisms by serum and erythrocyte membrane fatty acid composition ratios, shown by delta 6 and delta 5 desaturases (D6D and D5D, respectively), and also disease activities. The FADS2 gene with the rs174538 mutation affected D6D and D5D activities, with a greater effect on D5D. However, for disease activity, wild-type rs174538 was positively correlated with D6D activity. These results indicate that confirmation of the rs174538 mutation can be used to predict disease severity in CD cases.
