Analysis of variants and mutations in the human winged helix FOXA3 gene and associations with metabolic traits

D. C. Adler-Wailes, A. T. Alberobello, X. Ma, L. Hugendubler, E. A. Stern, Z. Mou, Joan Han, P. W. Kim, A. E. Sumner, J. A. Yanovski, E. Mueller

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background/Objectives: The forkhead factor Foxa3 is involved in the early transcriptional events controlling adipocyte differentiation and plays a critical function in fat depot expansion in response to high-fat diet regimens and during aging in mice. No studies to date have assessed the potential associations of genetic variants in FOXA3 with human metabolic outcomes. Subjects/Methods: In this study, we sequenced FOXA3 in 392 children, adolescents and young adults selected from several cohorts of subjects recruited at the National Institute of Child Health and Human Development of the National Institutes of Health based on the availability of dual-energy X-ray absorptiometry data, magnetic resonance imaging scans and DNA samples. We assessed the association between variants present in these subjects and metabolic traits and performed in vitro functional analysis of two novel FOXA3 missense mutations identified. Results: Our analysis identified 14 novel variants and showed that the common single-nucleotide polymorphism (SNP) rs28666870 is significantly associated with greater body mass index, lean body mass and appendicular lean mass (P values 0.009, 0.010 and 0.013 respectively). In vitro functional studies showed increased adipogenic function for the FOXA3 missense mutations c.185C > T (p.Ser62Leu) and c.731C > T (p.Ala244Val) compared with FOXA3-WT. Conclusions: Our study identified novel FOXA3 variants and mutations, assessed the adipogenic capacity of two novel missense alterations in vitro and demonstrated for the first time the associations between FOXA3 SNP rs28666870 with metabolic phenotypes in humans.

Original languageEnglish (US)
Pages (from-to)888-892
Number of pages5
JournalInternational Journal of Obesity
Volume39
Issue number6
DOIs
StatePublished - Jun 11 2015

Fingerprint

Missense Mutation
Mutation
Single Nucleotide Polymorphism
National Institute of Child Health and Human Development (U.S.)
Genes
Photon Absorptiometry
National Institutes of Health (U.S.)
High Fat Diet
Adipocytes
Young Adult
Body Mass Index
Fats
Magnetic Resonance Imaging
Phenotype
DNA
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Adler-Wailes, D. C., Alberobello, A. T., Ma, X., Hugendubler, L., Stern, E. A., Mou, Z., ... Mueller, E. (2015). Analysis of variants and mutations in the human winged helix FOXA3 gene and associations with metabolic traits. International Journal of Obesity, 39(6), 888-892. https://doi.org/10.1038/ijo.2015.17

Analysis of variants and mutations in the human winged helix FOXA3 gene and associations with metabolic traits. / Adler-Wailes, D. C.; Alberobello, A. T.; Ma, X.; Hugendubler, L.; Stern, E. A.; Mou, Z.; Han, Joan; Kim, P. W.; Sumner, A. E.; Yanovski, J. A.; Mueller, E.

In: International Journal of Obesity, Vol. 39, No. 6, 11.06.2015, p. 888-892.

Research output: Contribution to journalArticle

Adler-Wailes, DC, Alberobello, AT, Ma, X, Hugendubler, L, Stern, EA, Mou, Z, Han, J, Kim, PW, Sumner, AE, Yanovski, JA & Mueller, E 2015, 'Analysis of variants and mutations in the human winged helix FOXA3 gene and associations with metabolic traits', International Journal of Obesity, vol. 39, no. 6, pp. 888-892. https://doi.org/10.1038/ijo.2015.17
Adler-Wailes, D. C. ; Alberobello, A. T. ; Ma, X. ; Hugendubler, L. ; Stern, E. A. ; Mou, Z. ; Han, Joan ; Kim, P. W. ; Sumner, A. E. ; Yanovski, J. A. ; Mueller, E. / Analysis of variants and mutations in the human winged helix FOXA3 gene and associations with metabolic traits. In: International Journal of Obesity. 2015 ; Vol. 39, No. 6. pp. 888-892.
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