A at Single Nucleotide Polymorphism-358 is Required for G at -420 to Confer the Highest Plasma Resistin in the General Japanese Population

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2010 Mar 20

PMID 20300528

Citations 19

Authors

Hiroshi Onuma

Yasuharu Tabara

Ryoichi Kawamura

Takashi Tanaka

Jun Ohashi

Wataru Nishida

Yasunori Takata

Masaaki Ochi

Kazuya Yamada

Ryuichi Kawamoto

Katsuhiko Kohara

Tetsuro Miki

Hideichi Makino

Haruhiko Osawa

Affiliations

Soon will be listed here.

Abstract

Insulin resistance is a feature of type 2 diabetes. Resistin, secreted from adipocytes, causes insulin resistance in mice. We previously reported that the G/G genotype of single nucleotide polymorphism (SNP) at -420 (rs1862513) in the human resistin gene (RETN) increased susceptibility to type 2 diabetes by enhancing its promoter activity. Plasma resistin was highest in Japanese subjects with G/G genotype, followed by C/G, and C/C. In this study, we cross-sectionally analyzed plasma resistin and SNPs in the RETN region in 2,019 community-dwelling Japanese subjects. Plasma resistin was associated with SNP-638 (rs34861192), SNP-537 (rs34124816), SNP-420, SNP-358 (rs3219175), SNP+299 (rs3745367), and SNP+1263 (rs3745369) (P<10(-13) in all cases). SNP-638, SNP -420, SNP-358, and SNP+157 were in the same linkage disequilibrium (LD) block. SNP-358 and SNP-638 were nearly in complete LD (r(2) = 0.98), and were tightly correlated with SNP-420 (r(2) = 0.50, and 0.51, respectively). The correlation between either SNP-358 (or SNP-638) or SNP-420 and plasma resistin appeared to be strong (risk alleles for high plasma resistin; A at SNP-358, r(2) = 0.5224, P = 4.94x10(-324); G at SNP-420, r(2) = 0.2616, P = 1.71x10(-133)). In haplotypes determined by SNP-420 and SNP-358, the estimated frequencies for C-G, G-A, and G-G were 0.6700, 0.2005, and 0.1284, respectively, and C-A was rare (0.0011), suggesting that subjects with A at -358, generally had G at -420. This G-A haplotype conferred the highest plasma resistin (8.24 ng/ml difference/allele compared to C-G, P<0.0001). In THP-1 cells, the RETN promoter with the G-A haplotype showed the highest activity. Nuclear proteins specifically recognized one base difference at SNP-358, but not at SNP-638. Therefore, A at -358 is required for G at -420 to confer the highest plasma resistin in the general Japanese population. In Caucasians, the association between SNP-420 and plasma resistin is not strong, and A at -358 may not exist, suggesting that SNP-358 could explain this ethnic difference.

Citing Articles

Circulating resistin levels and mutation burden of the RETN gene variants predict long-term mortality in a Taiwanese population.

Hsu L, Teng M, Wu S, Liao M, Chou H, Ko Y Sci Rep. 2025; 15(1):564.

PMID: 39747951 PMC: 11695976. DOI: 10.1038/s41598-024-84142-4.

Interaction effect between low birthweight and resistin gene rs1862513 variant on insulin resistance and type 2 diabetes mellitus in adulthood: Toon Genome Study.

Yoshida A, Takata Y, Tabara Y, Maruyama K, Inoue S, Osawa H J Diabetes Investig. 2024; 15(6):725-735.

PMID: 38421160 PMC: 11143422. DOI: 10.1111/jdi.14163.

Genetically determined circulating resistin concentrations and risk of colorectal cancer: a two-sample Mendelian randomization study.

Pham T, Nimptsch K, Papadimitriou N, Aleksandrova K, Jenab M, Gunter M J Cancer Res Clin Oncol. 2023; 149(16):14889-14900.

PMID: 37599317 PMC: 10602946. DOI: 10.1007/s00432-023-05193-0.

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.

Hadate T, Kawamura R, Tabara Y, Maruyama K, Takakado M, Ikeda Y J Hum Genet. 2023; 68(11):745-750.

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

Resistin G-A haplotype at SNP-420/-358 is associated with the latent sarcopenic obesity index in the toon genome study.

Ikeda Y, Kawamura R, Takata Y, Tabara Y, Maruyama K, Takakado M J Diabetes Investig. 2023; 14(5):686-694.

PMID: 36897532 PMC: 10119914. DOI: 10.1111/jdi.13998.

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