4.7 Article

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

Journal

DIABETOLOGIA
Volume 47, Issue 10, Pages 1782-1788

Publisher

SPRINGER
DOI: 10.1007/s00125-004-1537-x

Keywords

genetics of Type 2 diabetes; genetic susceptibility; human genetics; non-insulin-dependent diabetes mellitus

Funding

  1. NHGRI NIH HHS [R01 HG000376, HG00376, T32 HG000040] Funding Source: Medline
  2. NIDDK NIH HHS [DK27619, DK62370, R01 DK062370, R01 DK029867, R01 DK027619, DK29867] Funding Source: Medline

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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. Our results add to growing evidence that resistin is associated with variation in weight, fat distribution and insulin resistance.

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