The FOX01A variation is rare and is unlikely to contribute to type 2 diabetes mellitus.

According to recent research from the United States, “The human forkhead box O1A (FOXO1A) gene on chromosome 13q14.1 is a key transcription factor in insulin signaling in liver and adipose tissue and plays a central role in the regulation of key pancreatic beta-cell genes including IPF1.”

M.A. Karim and colleagues at the University of Arkansas for Medical Sciences hypothesized “sequence variants of FOXO1A contribute to the observed defects in hepatic and peripheral insulin action and altered beta-cell compensation that characterize type 2 diabetes (T2DM). To test this hypothesis, we screened the three exons, 3’ untranslated region, and 5’ flanking region for sequence variants in Caucasian and African-American individuals with early onset (< 45 years) T2DM.”

They reported, “We identified only six variants; none altered the coding sequence, and except for one variant in the 3’ untranslated region, they were rare or absent in Caucasians.

To increase coverage of the gene, we selected seven additional variants in the large first intron and 5’ flanking region, thus providing 13 variants that spanned 116.4kb.

“Based on frequency and linkage disequilibrium patterns in a subset of individuals, we selected eight SNPs to type in a Caucasian population comprising 192 unrelated nondiabetic control individuals and 192 individuals with T2DM, and 10 SNPs to type in 182 controls and 352 diabetic individuals of African-American ancestry. No variant was associated with T2DM (African-Americans, p>0.08; Caucasians, p>0.09). Of the 8 Caucasian SNPs, six comprised a single haplotype block spanning over 100 kb and including most of the large first intron. In contrast, no block was observed among SNPs typed in African-Americans. No haplotype was associated with T2DM.”

The researchers concluded, “FOXO1A variation is rare and is unlikely to contribute to T2DM in either Caucasian or African-American populations.”

Karim and colleagues published their study in Molecular Genetics and Metabolism (Analysis of FOXO1A as a candidate gene for type 2 diabetes. Mol Genet Metab, 2006;88 (2):171-177).

For additional information, contact S.C. Elbein, University of Arkansas for Medical Sciences, College Medical, Dept. of Medical, Division Endocrinol & Metab, Little Rock, AR 72205, USA.

Publisher contact information for the journal Molecular Genetics and Metabolism is: Academic Press Inc. Elsevier Science, 525 B St., Ste. 1900, San Diego, CA 92101-4495, USA.