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

Toshimi Hadate; Ryoichi Kawamura; Yasuharu Tabara; Koutatsu Maruyama; Misaki Takakado; Yosuke Ikeda; Jun Ohashi; Yasunori Takata; Isao Saito; Haruhiko Osawa

doi:10.1038/s10038-023-01176-8

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. 2023 Nov;68(11):745-750. doi: 10.1038/s10038-023-01176-8. Epub 2023 Jul 10.

Authors

Affiliations

¹ Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan.
² Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.
³ Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
⁴ Department of Bioscience, Graduate School of Agriculture, Ehime University, Ehime, Japan.
⁵ Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan.
⁶ Department of Public Health and Epidemiology, Faculty of Medicine, Oita University, Oita, Japan.
⁷ Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan. harosawa@m.ehime-u.ac.jp.

PMID: 37423942
DOI: 10.1038/s10038-023-01176-8

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.