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Twin research shows glycan changes are more susceptible to environmental factors than their carrier glycoproteins

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Abstract

Changes in protein glycosylation are clinically used as biomarkers. In the present study, we employed a twin cohort to investigate the contributions of genetic and environmental factors to glycan modifications of glycoproteins. Mac-2 binding protein (Mac-2 bp), haptoglobin (Hp), and their glycosylated forms are liver fibrosis and cancer biomarkers. Sera from 107 twin pairs without clinical information were used as a training cohort for the Mac-2 bp and Mac-2 bp glycosylation isomer (M2BPGi) assay. As a validation cohort, 22 twin pairs were enrolled in the study. For each twin pair, one twin was diagnosed with liver or pancreatic disease. For the training cohort, the correlation ratios of serum Mac-2 bp and M2BPGi levels in twin sera with random sequences were 0.30 and 0.018, respectively. The correlation ratios between twin pairs in the validation cohort for serum Mac-2 bp and M2BPGi levels were 0.75 and 0.35, respectively. In contrast, correlation ratios of serum Hp and fucosylated haptoglobin (Fuc-Hp) levels between twin sera with liver and pancreatic disease were 0.49 and 0.16, respectively. Although serum protein levels of glycoproteins are susceptible to genetic factors, characteristic glycan changes of these glycoproteins are more susceptible to environmental factors, including liver and pancreatic disease.

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Abbreviations

ELISA:

Enzyme-linked immunosorbent assay

Hp:

Haptoglobin

Fuc-Hp:

Fucosylated haptoglobin

Mac-2 bp:

Mac-2 binding protein

M2BPGi:

Mac-2 binding protein glycosylation isomer

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Acknowledgements

We would like to thank the master course students for assaying for the biomarkers. We also thank Mr. Yudai Uenoyama at Sysmex Corporation for his support in performing the M2BPGi assay. The authors are also thankful to Beckman Coulter, Inc. (Tokyo, JAPAN) for the collaborative work.

Funding

Supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan (number 19H03562, 22H02967) and by a collaboration grant with Sysmex Corporation (number J770701645). This work was also supported by University Grants from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

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Authors and Affiliations

  1. Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Tatsuya Asuka, Koichi Morishita, Tomoya Fukuoka, Shinji Takamatsu, Jumpei Kondo & Eiji Miyoshi

  2. Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita, Osaka, 565–0871, Japan

    Yoshihiro Kamada

  3. Department of Clinical Laboratory and Biomedical Science, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Mikio Watanabe

  4. Laboratory of Child Healthcare and Genetic Science, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Norio Sakai

  5. Division of Health Science, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Kazuo Hayakawa

  6. Center for Twin Research, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Mikio Watanabe, Norio Sakai & Kazuo Hayakawa

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  1. Tatsuya Asuka
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Osaka Twin Research Group

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Correspondence to Eiji Miyoshi.

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Conflict of interest

We have a collaborative grant with Sysmex Corporation.

Ethical approval

The ethical committee at Osaka University Hospital approved the study protocol (protocol IDs 696 and 19389).

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Supplementary information

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10719_2023_10099_MOESM1_ESM.docx

Supplementary Fig. 1 Correlation of Mac-2 bp and M2BPGi in the training cohort. A and B Comparison of serum (A) Mac-2 bp levels and (B) M2BPGi levels of each of the 107 twin pairs using random change correlation method (method 1). C and D Comparison of serum (C) Mac-2 bp levels and (D) M2BPGi levels of each of the 107 twin pairs using comparative method of high score on the Y-axis and the low score on the X-axis (method 2) (DOCX 54 KB)

10719_2023_10099_MOESM2_ESM.docx

Supplementary Fig. 2 Correlation of Mac-2 bp and M2BPGi in the training cohort, not including cases with high Mac-2 bp expression (M2BPGi > 3.0 or Mac-2 bp > 6.0 µg/ml). A and B Comparison of serum (A) Mac-2 bp levels and (B) M2BPGi levels of each of the 102 twin pairs not including cases with high Mac-2 bp expression using random change correlation method (method 1). C and D Comparison of serum (C) Mac-2 bp levels and (D) M2BPGi levels of each of the 102 twin pairs not including cases with high Mac-2 bp expression using comparative method of high score on the Y-axis and the low score on the X-axis (method 2). (DOCX 59 KB)

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Asuka, T., Kamada, Y., Morishita, K. et al. Twin research shows glycan changes are more susceptible to environmental factors than their carrier glycoproteins. Glycoconj J 40, 191–198 (2023). https://doi.org/10.1007/s10719-023-10099-7

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