Variation in the resistin gene is associated with obesity and insulin-related phenotypes in Finnish subjects.
OBJECTIVE
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.
Conneely
K N
KN
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109-2029, USA.
Silander
K
K
Scott
L J
LJ
Mohlke
K L
KL
Lazaridis
K N
KN
Valle
T T
TT
Tuomilehto
J
J
Bergman
R N
RN
Watanabe
R M
RM
Buchanan
T A
TA
Collins
F S
FS
Boehnke
M
M
D020413:3' Untranslated Regions / Q000235:genetics; D017668:Age of Onset; D000368:Aged; D000465:Algorithms; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D014644:Genetic Variation; D005838:Genotype; D006729:Hormones, Ectopic / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology* / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D052243:Resistin
D020413:3' Untranslated Regions; D006729:Hormones, Ectopic; D007328:Insulin; C499624:RETN protein, human; D052243:Resistin