Polymorphisms in FOXO gene family and association analysis with BMI.

Forkhead transcription factors of the FOXO subfamily are emerging as shared components of pathways that regulate a variety of cellular functions. In an effort to identify genetic polymorphisms in candidate genes to determine associations with BMI, we sequenced all exons of the FOXO genes (FOXO1a, FOXO3a, and FOXO4) and examined their associations with BMI in a Korean population (n = 734). Sixteen polymorphisms were identified in FOXO genes: three in FOXO1a, seven in FOXO3a, and six in FOXO4. Associations of FOXO polymorphisms with BMI were analyzed using multiple regression, adjusting for age and sex as covariates. One promoter single nucleotide polymorphism in the 5' flanking region of FOXO3a showed significant association with BMI, e.g., the lowest BMI (23.3 +/- 2.69 kg/m2) was discovered in individuals who were carrying T/T, intermediate BMI (26.6 +/- 3.14 kg/m2) was found in heterozygous individuals (C/T), and the highest BMI (27.2 +/- 3.47 kg/m2) occurred in individuals who were homozygous for the major allele (C/C; p = 0.01).