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Visit to visit transition in TXNIP gene methylation and the risk of type 2 diabetes mellitus: a nested case-control study

Abstract

Our study aimed to investigate the association between the transition of the TXNIP gene methylation level and the risk of incident type 2 diabetes mellitus (T2DM). This study included 263 incident cases of T2DM and 263 matched non-T2DM participants. According to the methylation levels of five loci (CpG1–5; chr1:145441102-145442001) on the TXNIP gene, the participants were classified into four transition groups: maintained low, low to high, high to low, and maintained high methylation levels. Compared with individuals whose methylation level of CpG2–5 at the TXNIP gene was maintained low, individuals with maintained high methylation levels showed a 61–87% reduction in T2DM risk (66% for CpG2 [OR: 0.34, 95% CI: 0.14, 0.80]; 77% for CpG3 [OR: 0.23, 95% CI: 0.07, 0.78]; 87% for CpG4 [OR: 0.13, 95% CI: 0.03, 0.56]; and 61% for CpG5 [OR: 0.39, 95% CI: 0.16, 0.92]). Maintained high methylation levels of four loci of the TXNIP gene are associated with a reduction of T2DM incident risk in the current study. Our study suggests that preserving hypermethylation levels of the TXNIP gene may hold promise as a potential preventive measure against the onset of T2DM.

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Funding

This study was supported by the National Natural Science Foundation of China (grant nos. 82304228, 82073646, 81973152, 82103940, and 82273707), the Postdoctoral Research Foundation of China (grant no. 2021M692903), the Key R&D and promotion projects in Henan Province (grant no. 232102311017), Guangdong Basic and Applied Basic Research Foundation (grant nos. 2021A1515012503 and 2022A1515010503), the Shenzhen Science and Technology Program (grant nos. JCYJ20210324093612032 and JCYJ20220818095818040), and Nanshan District Science and Technology Program Key Project of Shenzhen (grant no. NS2022009).

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YW and WC substantially contributed to the design and drafting of the study and the analysis and interpretation of the data; YW wrote the manuscript; YZ, MG, YG, YK, LW, MW, WZ, YC, WH, XF, XL, DZ, PQ, and FH contributed to data acquisition; and DH, YL, XS, and MZ revised it critically for important intellectual content. All authors have read and approved the submission of the manuscript.

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Correspondence to Dongsheng Hu.

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This study was approved by the Medical Ethics Committee of Shenzhen University Health Science Center. Informed consent was obtained from each study participant before enrollment in this study.

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Wu, Y., Chen, W., Zhao, Y. et al. Visit to visit transition in TXNIP gene methylation and the risk of type 2 diabetes mellitus: a nested case-control study. J Hum Genet 69, 311–319 (2024). https://doi.org/10.1038/s10038-024-01243-8

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