Plasma resistin is associated with single nucleotide polymorphisms of a possible resistin receptor, the decorin gene, in the general Japanese population

Abstract

Resistin is an adipokine secreted from adipocytes in mice. We previously reported that a single nucleotide polymorphism (SNP) -420 (rs1862513) in the human resistin gene (RETN), is correlated with plasma resistin. Decorin is a multifunctional proteoglycan, and its isoform, lacking 14 amino acids from the N terminal region of mature core decorin, recently was identified as a resistin receptor in mice. To examine whether SNPs in the vicinity of the human decorin gene (DCN) are associated with plasma resistin, we cross-sectionally analyzed six tag SNPs selected around DCN in the same linkage disequilibrium block in 2,078 community-dwelling Japanese subjects. Plasma resistin was associated with the rs7139228, rs7956537, rs516115, and rs3138167 genotypes in DCN. A multiple regression analysis revealed that the genotype of rs7308752 (G/G) or rs516115 (C/C) was associated with decreased plasma resistin after adjusted for age, sex, BMI, and the RETN SNP rs1862513. The effect of rs7139228 and rs1862513 seemed to be additive without synergistic interaction. Therefore, plasma resistin was associated with some tag SNPs around DCN in the general Japanese population. The possibility that human decorin is a human resistin receptor should be pursued.

FIG. 1.

The six tag SNPs around DCN analyzed were in the same LD and were genotyped in 2,078 subjects in the general Japanese population. LD between each pair of these SNPs were analyzed using Haploview software (17). The LD block consisting of these six SNPs was defined by the confidence interval analysis. Each square represents a pairwise value of Dʹ, with the standard gradation (black box indicates logarithm of odds (LOD) ≥2 and D' = 1; boxes with no number indicate LOD <2 and D'=1; white boxes indicate LOD < 2 and Dʹ < 1; and gray boxes indicate LOD ≥2 and D' < 1). Numbers in the shaded squares are the r² values between each pair of SNPs. Two SNPs are located in the intron of DCN, and four SNPs are located in the intergenic region of DCN.

FIG. 2.

Plasma resistin according to the DCN rs7139228 genotype and RETN rs1862513 genotype. Plasma resistin according to DCN rs7139228 (GA+AA and GG) and RETN rs1862513 genotype (CC, CG, and GG) is shown. Values are means ± SD. The numbers of subjects are shown in the columns. Interaction between the DCN rs7139228 and RETN rs1862513 genotypes were assessed by ANCOVA.