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Protein arginine N-methyltransferase 1 gene polymorphism is associated with proliferative diabetic retinopathy in a Japanese population

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Abstract

Aims

To investigate the effects of single-nucleotide polymorphisms (SNPs) around the protein arginine N-methyltransferase 1 (PRMT1) gene on the incidence and severity of diabetic retinopathy (DR).

Methods

A total of 310 Japanese patients with type 2 diabetes mellitus (T2DM) were investigated. Genotyping of ten tagged SNPs were performed by quantitative real-time polymerase chain reaction (qRT-PCR). The association between each SNP genotype and diabetic microangiopathy was assessed using univariate analysis in a dominant model of the minor alleles followed by multivariate logistic regression analysis with the propensity score matching (PSM) method. The effect of disease-related SNP on PRMT1 and hypoxia-inducible factor-1α (HIF-1α) mRNA levels in vivo was evaluated by qRT-PCR.

Results

In the univariate analysis, the minor A allele at rs374569 and the minor C allele at rs3745468 were associated with DR severity (P = 0.047 and P = 0.003, respectively), but not diabetic nephropathy and peripheral polyneuropathy severity. Multivariate analysis showed that the rs3745468 variant caused an increased incidence of proliferative DR (PDR) (odds ratio 9.37, 95% confidence interval 1.12–78.0, P = 0.039). In the PSM cohort, the patients carrying the rs3745468 variant had lower PRMT1 mRNA levels compared to those without the variant (P = 0.037), and there was an inverse correlation between PRMT1 and HIF-1α mRNA levels (r = −0.233, P = 0.035).

Conclusions

The rs3745468 variant in the PRMT1 gene was associated with an increased incidence of PDR in Japanese patients with T2DM and might be involved in the HIF-1-dependent hypoxic pathway through altered PRMT1 levels.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank all the subjects involved in the study. The authors appreciate the department of ophthalmology at Toshiba Rinkan Hospital for performing the ophthalmic evaluation and are also grateful to the medical staffs at Toshiba Rinkan Hospital for their cooperation in collecting blood samples, measuring clinical laboratory tests and performing nerve conduction velocity studies.

Funding

This work was supported in part by research grant from the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan to Masayoshi Shichiri (18H05383, 20K20389).

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Toshiba Rinkan Hospital, 7-9-1 Kami-tsuruma, Minami-ku, Sagamihara, Kanagawa, 252-0385, Japan

    Hiroaki Iwasaki

  2. Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, Sagamihara, Japan

    Hiroaki Iwasaki & Masayoshi Shichiri

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  1. Hiroaki Iwasaki
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Contributions

All authors contributed to the conception and design of the study. Hiroaki Iwasaki performed the acquisition of data and the interpretation of the results by statistical analysis, and wrote the manuscript. Masayoshi Shichiri was involved in the research initiative, supervised research works in the laboratory and reviewed the manuscript. All authors have given their final approval of the posted version. Hiroaki Iwasaki is responsible for the integrity of the work as a whole.

Corresponding author

Correspondence to Hiroaki Iwasaki.

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Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical approval

The present study was approved by the Ethic Committee of Toshiba Rinkan Hospital held on 26 February 2018. The protocols were in compliance with the Declaration of Helsinki. All procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent

Written informed consent for being included in the study and regarding the publication of the study content was obtained from all subjects before the commencement of the study.

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This article belongs to the topical collection Eye Complications of Diabetes, managed by Giuseppe Querques.

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Iwasaki, H., Shichiri, M. Protein arginine N-methyltransferase 1 gene polymorphism is associated with proliferative diabetic retinopathy in a Japanese population. Acta Diabetol 59, 319–327 (2022). https://doi.org/10.1007/s00592-021-01808-5

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  • DOI: https://doi.org/10.1007/s00592-021-01808-5

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