Korean Diabetes Journal 2004;28(1):9-19.
Published online February 1, 2004.
Common Genetic Polymorphisms in the Promoter of Resistin Gene are Major Determinants of Plasma Resistin Concentrations in Humans.
Young Min Cho, Byung Soo Youn, Sung Soo Chung, Ki Woo Kim, Bo Kyeong Koo, Kang Yeol Yu, Hong Je Park, Hyoung Doo Shin, Hak Chul Jang, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee
1Department of Internal Medicine, Seoul National University College of Medicine, Korea.
2Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Korea.
3KOMED Institute for Life Science, Graduate School of Biotechnology, Korea University, Korea.
4Department of Genetic Epidemiology, SNP Genetics, Inc., Korea.
Abstract
BACKGROUND
Resistin has been postulated to be an important link between obesity and insulin resistance. Genetic polymorphisms in the resistin gene promotor have been suggested as a determinant of the expression of resistin mRNA, which is possibly associated with obesity and insulin resistance. In this study, the association between the genotype of the resistin promoter, and its plasma concentrations, were investigated. METHODS: The g.-537A>C and g.-420C>G polymorphisms in the resistin promoter were examined, and the levels of plasma resistin measured in the Korean subjects, both with and without type 2 diabetes. Haplotype-based promoter activity and the gel electrophoretic mobility-shift assays(EMSA) were also performed. RESULTS: The -420G and the -537A alleles, which were in linkage disequilibrium, were associated with higher plasma resistin concentrations. Individuals with the A-G(-537 A and -420G) haplotypes showed significantly higher plasma resistin levels than those that did not. The haplotypes A-G had modestly increased promoter activities compared to the other haplotypes. The EMSA revealed the -420 G allele to be specific for binding of the nuclear proteins from adipocytes and monocytes. However, neither polymorphism was associated with type 2 diabetes or obesity in our study subjects. CONCLUSION: Polymorphisms in the promoter of the resistin gene are major determinants of plasma resistin concentrations in humans
Key Words: Resistin, Plasma concentration, Promoter, Genotype, Diabetes
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