Common genetic polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans

Abstract

Aims/hypothesis. Resistin is thought to be an important link between obesity and insulin resistance. It has been suggested that genetic polymorphism in the promoter of resistin gene is a determinant of resistin mRNA expression and possibly associated with obesity and insulin resistance. In this study, we investigated the association between the genotype of resistin promoter and its plasma concentrations. Methods. We examined g.-537A>C and g.-420C>G polymorphisms in the resistin promoter and measured plasma resistin concentrations in Korean subjects with or without Type 2 diabetes. We also did haplotypebased promoter activity assays and the gel electrophoretic mobility shift assay. Results. The −420G and the −537A alleles, which were in linkage disequilibrium, were associated with higher plasma resistin concentrations. Individuals with haplotype A-G (−537A and −420G) had significantly higher plasma resistin concentrations than the others. Haplotype A-G had modestly increased promoter activity compared to the other haplotypes. Electrophoretic mobility shift assay showed that the −420G allele is specific for binding of nuclear proteins from adipocytes and monocytes. However, none of the two polymorphisms were associated with Type 2 diabetes or obesity in our study subjects. Conclusions/interpretation. Polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans. [Diabetologia (2004) . Moreover, obese mice given an antiresistin antibody had increased insulin-stimulated glucose uptake, whereas the treatment of normal mice with recombinant resistin impaired insulin action [4]. Resistin therefore could link obesity with insulin resistance and diabetes in mouse models. However, subsequent studies in rodent models have produced disparate findings on the role of resistin in obesity and insulin resistance [5,6,7].In humans, the expression of resistin in adipocytes is much lower than that seen in rodents and does not differ between normal, insulin-resistant or Type 2 diabetic patients [8,9,10]. Little is known about the relationship between circulating resistin concentrations Resistin belongs to a novel family of cystein-rich C-terminal domain proteins called resistin-like molecules, which are identical to those found in inflammatory

Regulation of human resistin gene expression in cell systems: an important role of stimulatory protein 1 interaction with a common promoter polymorphic site

“…We also reported that this polymorphism was important in determining plasma resistin levels [21]. In that study, plasma resistin levels of the −420G/G genotype group were higher than those of the −420C/C genotype group.…”

“…Several polymorphisms have been found in the promoter region of the resistin gene and it has been reported that one polymorphism, −420 C>G, was related to plasma resistin levels and diabetes [20,21,30]. In this study, we investigated the molecular mechanism underlying the effect of the −420G/C variation on the expression of the resistin gene.…”

“…Three specific DNA-protein complexes (bands 1, 2 and 3) and free probes are indicated. The −420G/C variation-independent band is indicated by an asterisk, and the fact that this band is not related to the −420G/C variation was proven in the previous work [21] of resistin in the media was measured using a mouse resistin ELISA kit according to the manufacturer's instructions (Komed, Seoul, Korea) [11].…”

“…In that study, plasma resistin levels of the −420G/G genotype group were higher than those of the −420C/C genotype group. In addition, we showed that the specific transcription factors of the nuclear extracts from adipocytes and monocytes were bound to the −420G region with high affinity but not to the −420C region [21].…”

Absence of evidence for an association between resistin gene variants and insulin resistance in an Asian population with low and high blood pressure

“…For example, although many studies report a lack of association between resistin gene variants and type 2 diabetes [4][5][6]10,[20][21][22][23][24][25], only one of these analyzed a sample population larger than 1000 subjects [4]. When data from three of the negative result studies [20][21][22] were analyzed together with new samples in a meta-analysis of 3536 subjects, the combined results showed an association between the −420C>G variant (RETN5) and diabetes [26].…”