Common genetic polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans.
OBJECTIVE
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 haplotype-based 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
Polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans.
Cho
Y M
YM
Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong Chongno-Gu, Seoul, 110-744, Korea.|Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
Youn
B-S
BS
KOMED Institute for Life Science, Graduate School of Biotechnology, Korea University, Seoul, Korea.
Chung
S S
SS
Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
Kim
K W
KW
Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
Lee
H K
HK
Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong Chongno-Gu, Seoul, 110-744, Korea.
Yu
K-Y
KY
KOMED Institute for Life Science, Graduate School of Biotechnology, Korea University, Seoul, Korea.
Park
H J
HJ
KOMED Institute for Life Science, Graduate School of Biotechnology, Korea University, Seoul, Korea.
Shin
H D
HD
Department of Genetic Epidemiology, SNP Genetics, Seoul, Korea.
Park
K S
KS
Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong Chongno-Gu, Seoul, 110-744, Korea. kspark@snu.ac.kr.|Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea. kspark@snu.ac.kr.
D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006729:Hormones, Ectopic / Q000097:blood* / Q000235:genetics*; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012016:Reference Values; D052243:Resistin
D006729:Hormones, Ectopic; C499624:RETN protein, human; D052243:Resistin