Genetic variation in the human winged helix/forkhead transcription factor gene FOXC2 in Pima Indians.
ABSTRACT FOXC2 is a winged helix gene that has been shown to counteract obesity, hypertriglyceridemia, and diet-induced insulin resistance in rodents. Therefore, FOXC2 was analyzed as a candidate gene for susceptibility to type 2 diabetes in Pima Indians. Four variants were identified by sequencing the coding region, as well as 638 bp of the 5' region and 300 bp of the 3' region of the gene. Two single nucleotide polymorphisms (SNPs) were found in the putative promoter region, a C-512T transition and a G-350T. In addition, two SNPs were found in the 3' region, a C1548T and a C1702T. The G-350T and the C1702T variants were in complete linkage disequilibrium, and the C1548T variant was relatively rare; therefore, only the C-512T and G-350T variants were additionally genotyped in 937 full-blooded Pima Indians. Neither of these polymorphisms were associated with type 2 diabetes; however, the C-512T variant was associated with BMI (P = 0.03) and percentage of body fat (P = 0.02) in male and female Pima subjects, as well as with basal glucose turnover and fasting plasma triglycerides in women. Our data indicate that variation in FOXC2 may have a minor role in body weight control and seems to be involved in the regulation of basal glucose turnover and plasma triglyceride levels in women, but this gene does not significantly contribute to the etiology of type 2 diabetes in Pima Indians.
- SourceAvailable from: S John Weisnagel[Show abstract] [Hide abstract]
ABSTRACT: This report constitutes the seventh update of the human obesity gene map incorporating published results up to the end of October 2000. Evidence from the rodent and human obesity cases caused by single-gene mutations, Mendelian disorders exhibiting obesity as a clinical feature, quantitative trait loci uncovered in human genome-wide scans and in cross-breeding experiments in various animal models, and association and linkage studies with candidate genes and other markers are reviewed. Forty-seven human cases of obesity caused by single-gene mutations in six different genes have been reported in the literature to date. Twenty-four Mendelian disorders exhibiting obesity as one of their clinical manifestations have now been mapped. The number of different quantitative trait loci reported from animal models currently reaches 115. Attempts to relate DNA sequence variation in specific genes to obesity phenotypes continue to grow, with 130 studies reporting positive associations with 48 candidate genes. Finally, 59 loci have been linked to obesity indicators in genomic scans and other linkage study designs. The obesity gene map reveals that putative loci affecting obesity-related phenotypes can be found on all chromosomes except chromosome Y. A total of 54 new loci have been added to the map in the past 12 months and the number of genes, markers, and chromosomal regions that have been associated or linked with human obesity phenotypes is now above 250. Likewise, the number of negative studies, which are only partially reviewed here, is also on the rise.Obesity research 02/2001; 9(2):135-69. · 4.95 Impact Factor
Article: On the generators of SP n ( Z )[Show abstract] [Hide abstract]
ABSTRACT: We give a short variant of the classical proofs for the generation of the symplectic group Spn(Z) over Z by the standard matrices.Linear Algebra and its Applications 01/1997; 253(1):363-367. · 0.98 Impact Factor