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Diabetes 52:562-567, 2003
© 2003 by the American Diabetes Association, Inc.

Brief Genetics Reports

Systematic Search for Single Nucleotide Polymorphisms in the FOXC2 Gene

The Absence of Evidence for the Association of Three Frequent Single Nucleotide Polymorphisms and Four Common Haplotypes 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

1 Department of Laboratory Medicine, Ehime University School of Medicine, Ehime, Japan
2 Ehime Prefectural Hospital, Ehime, Japan
3 Department of Human Genetics, School of International Health, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan

FOXC2, a forkhead/winged helix transcription factor, represents a promising candidate gene for type 2 diabetes since transgenic mice that specifically overexpress this gene in adipocytes are lean and insulin sensitive. To determine whether there are single nucleotide polymorphisms (SNPs) in this gene that are associated with type 2 diabetes, sequences of the coding and ~1 kb of 5' flanking regions in 24 Japanese type 2 diabetic subjects were initially analyzed using PCR direct sequencing, and the regions containing the identified polymorphisms were then examined. In 200 control subjects, three frequent SNPs were found (g. -512C>T [32.3%] and -350G>T [13.0%] in the 5' flanking region and +1548C>T [10.0%] in the 3' flanking region). Linkage disequilibria were found between all three pairs of these SNPs. Of the eight possible haplotypes defined by these SNPs, only four were found. When the frequencies of these SNPs and the four common haplotypes between 195 type 2 diabetic and 200 control subjects were compared, no association was evident. The +898C>T (Pro300Ser), +907C>A (Leu303Met), 1167_1169delCCA (389delHis), and +1251C>A (Ala417Ala) identified in the coding region were rare, although +907C>A could be higher in type 2 diabetic subjects (1.5%) than in control subjects (0.3%). Thus, the SNPs identified in the FOXC2 gene are unlikely to have major effects on susceptibility to Japanese type 2 diabetes.


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P. Kovacs, A. Lehn-Stefan, M. Stumvoll, C. Bogardus, and L. J. Baier
Genetic Variation in the Human Winged Helix/Forkhead Transcription Factor Gene FOXC2 in Pima Indians
Diabetes, May 1, 2003; 52(5): 1292 - 1295.
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