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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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.
The authors declare no competing interests.
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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