Novel resistin promoter polymorphisms: association with serum resistin level in Japanese obese individuals.
OBJECTIVE
Resistin, an adipocyte-secreted cytokine recently discovered in mice, has been proposed as a link between obesity and diabetes. We analyzed resistin gene polymorphisms and examined their association with serum resistin level and obesity phenotypes in humans.


METHODS
Sixty young, obese, non-diabetic subjects taking no medication were studied. DNA sequencing and genotyping of identified single nucleotide polymorphisms were performed. Associations between polymorphisms and serum resistin level, BMI, body composition, fat distribution, and several indices of insulin sensitivity were examined. Moreover, single nucleotide polymorphisms in the promoter region were examined for their influence on resistin gene transcriptional activity using luciferase reporter vectors.


RESULTS
Ten non-coding single nucleotide polymorphisms were found. The -638G>A, -420C>G, and -358G>A polymorphisms in the promoter region showed marked linkage disequilibrium with each other, and were associated with serum resistin level; however, there was no association between these polymorphisms and parameters related to adiposity or insulin resistance. The results of luciferase assay revealed that -638G>A together with the -420C>G polymorphism influenced resistin gene transcriptional activity.


CONCLUSIONS
We found that variability in the serum resistin level might be related to polymorphic variants of the promoter region of the gene.
Department of Internal Mecicine, School of Medicine, Keio University, Tokyo, Japan. SNA12474@nifty.com
K
K
Azuma
S
S
Oguchi
Y
Y
Matsubara
T
T
Mamizuka
M
M
Murata
H
H
Kikuchi
K
K
Watanabe
F
F
Katsukawa
H
H
Yamazaki
A
A
Shimada
T
T
Saruta
D000225:Adenine; D000328:Adult; D044466:Asian People / Q000235:genetics*; D003596:Cytosine; D005260:Female; D006147:Guanine; D006729:Hormones, Ectopic / Q000097:blood* / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009765:Obesity / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D052243:Resistin; D014158:Transcription, Genetic
D006729:Hormones, Ectopic; C499624:RETN protein, human; D052243:Resistin; D006147:Guanine; D003596:Cytosine; D000225:Adenine