Systematic Search for Single Nucleotide Polymorphisms in the Resistin Gene
The Absence of Evidence for the Association of Three Identified Single Nucleotide Polymorphisms With Japanese Type 2 Diabetes
- Haruhiko Osawa1,
- Hiroshi Onuma1,
- Akiko Murakami1,
- Masaaki Ochi1,
- Tatsuya Nishimiya1,
- Kenichi Kato2,
- Ikki Shimizu2,
- Yasuhisa Fujii2,
- Jun Ohashi3 and
- Hideichi Makino1
- 1Department of Laboratory Medicine, Ehime University School of Medicine, Ehime, Japan
- 2Ehime Prefectural Hospital, Ehime, Japan
- 3Department of Human Genetics, School of International Health, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
Resistin is a novel polypeptide specifically secreted from adipocytes, and its serum levels are increased in obese diabetic mice. Resistin antagonizes insulin and could account for insulin resistance. To determine whether there are single nucleotide polymorphisms (SNPs) in the resistin gene associated with type 2 diabetes, sequences for 24 Japanese type 2 diabetic patients were initially analyzed using PCR direct sequencing. Three SNPs were found in the introns, but none were present in the coding regions. The allele frequencies of genomic −167C>T, +157C>T, and +299G>A in 99 Japanese control subjects were determined to be 3.5, 6.6, and 39.4%, respectively. In each pair of these SNPs, linkage disequilibria were found between either −167C>T and +299G>A or +157C>T and +299G>A. A linkage disequilibrium was also detected among −167C>T, +157C>T, and +299G>A, and only four of the eight possible haplotypes defined by these SNPs were found. A comparison of the frequencies of these SNPs and haplotypes between 99 type 2 diabetes and 99 control subjects revealed no evidence for any association. These identified SNPs, which were in linkage disequilibrium, represent potentially useful tools for searching for their association with specific phenotypes of diabetes.
Address correspondence and reprint requests to Dr. H. Osawa, Department of Laboratory Medicine Ehime University School of Medicine, Shigenobu, Ehime 791-0295, Japan. E-mail:.
Received for publication 29 August 2001 and accepted in revised form 19 November 2001.
PPAR-γ, peroxisome proliferator–activated receptor-γ; RELM, resistin-like molecule; SNP, single nucleotide polymorphism.