Variation in the resistin gene is associated with obesity and insulin-related phenotypes in Finnish subjects

Abstract

Aims/hypothesis. Resistin is a peptide hormone produced by adipocytes that is present at high levels in sera of obese mice and may be involved in glucose homeostasis through regulation of insulin sensitivity. Several studies in humans have found associations between polymorphisms in the resistin gene and obesity, insulin sensitivity and blood pressure. An association between variation in the resistin gene and Type 2 diabetes has been reported in some, but not all studies. The aim of this study was to analyse variants of the resistin gene for association with Type 2 diabetes and related traits in a Finnish sample. Methods. In 781 cases with Type 2 diabetes, 187 spouse controls and 222 elderly controls of Finnish origin, we genotyped four previously identified non-coding single-nucleotide polymorphisms (SNPs): -420C>G from the promoter region, +156C>T and +298G>A from intron 2, and +1084G>A from the 3′ untranslated region. We then tested whether these SNPs were associated with Type 2 diabetes and related traits. Results. The SNPs were not significantly associated with Type 2 diabetes. However, SNPs −420C>G, +156C>T and +298G>A and the common haplotype for these three markers were associated with increased values of weight-related traits and diastolic blood pressure in cases, lower weight in elderly control subjects, and lower insulin sensitivity and greater acute insulin response in spouses. Furthermore, the +1084G allele was associated with lower HDL cholesterol in both cases and controls, higher systolic blood pressure and waist circumference in cases, and greater acute insulin response in spouse controls. Conclusions/interpretation. Our results add to growing evidence that resistin is associated with variation in weight, fat distribution and insulin resistance.

The CC genotype of the GNAS T393C polymorphism is associated with obesity and insulin resistance in women with polycystic ovary syndrome

“…Defects in the melanocortin pathway are related to severe obesity (12). Similar results were obtained for leptin receptor mutations (13), variations of the resistin gene (14), and the adiponectin locus (15). In Germans, Chinese, and South Africans, the 825T allele of the gene GNB3 encoding the G-protein b3 subunit is significantly associated with obesity with odds ratios (ORs) between 2 and 3 (16).…”

Hyperleptinaemia rather than fasting hyperinsulinaemia is associated with obesity following hypothalamic damage in children

“…Adiponectin is produced predominantly by peripheral adipose tissue, and resistin is produced by visceral adipose tissue. Adiponectin improves insulin sensitivity whereas resistin worsens it in rodent studies (16,17), with conflicting results in humans (18)(19)(20). Although a recent study by Meigs and colleagues did demonstrate that insulin resistance in humans was inversely related to adiponectin and positively related to resistin (21).…”

Regulation of insulin signalling, glucose uptake and metabolism in rat skeletal muscle cells upon prolonged exposure to resistin

“…Furthermore, although some studies suggest a link between resistin and insulin sensitivity [19] others have failed to show an association with insulin resistance [16,20,21]. Similarly, genetic analyses have suggested that resistin plays a role in the aetiology of insulin resistance and diabetes [22,23], whereas others contest this view [24].…”