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Positive association between serum resistin and smoking was strongest in homozygotes of the G-A haplotype at c.-420 C>G and c.-358 G>A in RETN promoter: the Toon Genome Study

Journal of Human Genetics volume 68, pages 745–750 (2023)Cite this article

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Abstract

Resistin is mainly expressed in human monocytes/macrophages and is associated with insulin resistance, inflammation, and atherosclerosis. Serum resistin is strongly correlated with the G-A haplotype defined by single nucleotide polymorphisms (SNPs) c.-420 C>G (SNP-420) (rs1862513) and c.-358 G>A (SNP-358) (rs3219175) in the promoter region of the human resistin gene (RETN). Smoking is also associated with insulin resistance. We investigated the association between smoking and serum resistin and the effect of the G-A haplotype on this association. Participants were recruited under the Toon Genome Study (an observational epidemiology research in the Japanese population). Of these, 1975 subjects genotyped for both SNP-420 and SNP-358 were analyzed for serum resistin by grouping them based on smoking status and G-A haplotype status. RETN mRNA, isolated from whole blood cells, was evaluated in smokers (n = 7) and age-, sex-, and BMI-matched non-smokers (n = 7) with the G-A haplotype homozygotes. Serum resistin tended to be higher in current smokers who smoked more cigarettes per day (P for trend < 0.0001). The positive association between serum resistin and smoking was strongest in the G-A haplotype homozygotes, followed by heterozygotes and non-carriers (interaction P < 0.0001). This positive association was stronger in the G-A homozygotes than the C-G homozygotes (interaction P < 0.0001). RETN mRNA was 1.40-fold higher in smokers than non-smokers with the G-A homozygotes (P = 0.022). Therefore, the positive association between serum resistin and smoking was strongest in the G-A haplotype homozygotes defined by RETN SNP-420 and SNP-358.

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Acknowledgements

This work was supported by JSPS KAKENHI, grants from Ehime University, and by support from Mr. Takeshi Ikeda. The authors wish to thank all the members in the department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine for critical discussions. We are also grateful to all the staff members associated with this study, especially Ms. Otaki, Ms. Kagawa, and Dr. Sano, for supporting the medical check-ups and technical assistance.

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Authors and Affiliations

  1. Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan

    Toshimi Hadate, Ryoichi Kawamura, Misaki Takakado, Yosuke Ikeda, Yasunori Takata & Haruhiko Osawa

  2. Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan

    Yasuharu Tabara

  3. Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Yasuharu Tabara

  4. Department of Bioscience, Graduate School of Agriculture, Ehime University, Ehime, Japan

    Koutatsu Maruyama

  5. Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan

    Jun Ohashi

  6. Department of Public Health and Epidemiology, Faculty of Medicine, Oita University, Oita, Japan

    Isao Saito

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  1. Toshimi Hadate
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Contributions

TH designed the experiments, researched and analyzed data, and wrote the manuscript. RK designed the experiments, researched data, contributed to discussion, reviewed and edited the manuscripts. YTab and JO conducted statistical analyses, contributed to discussion, and reviewed the manuscripts. KM, MT, YI, and IS contributed to discussion, and reviewed the manuscripts. YTak designed the experiments, researched data, contributed to discussion, and reviewed the manuscripts. HO designed the experiments, contributed to discussion, and reviewed and edited the manuscripts. HO is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Haruhiko Osawa.

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Hadate, T., Kawamura, R., Tabara, Y. et al. Positive association between serum resistin and smoking was strongest in homozygotes of the G-A haplotype at c.-420 C>G and c.-358 G>A in RETN promoter: the Toon Genome Study. J Hum Genet 68, 745–750 (2023). https://doi.org/10.1038/s10038-023-01176-8

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