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ZFP36: a Promising Candidate Gene for Obesity-Related Metabolic Complications Identified by Converging Genomics

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Background

Few genes have been associated with the metabolic syndrome (MS), although its genetic component is well accepted. The aim of this study was to compare the adipose tissue gene expression profiles of obese men with and without the MS and to apply an integrative genomic approach to propose new candidate genes.

Methods

Affymetrix HG-U133 plus 2 arrays have been used for expression profiling of omental adipose tissue of non-diabetic obese men with (n=7) and without (n=7) the MS, as defined by the NCEP-ATPIII, that undergo a bariatric operation.

Results

Omentum expresses a total of 23 055 transcripts. Overall, 489 genes were differentially expressed between the two groups. A total of 80 differentially expressed genes were located within a previously identified region of linkage. In this subset of genes, zinc finger protein 36 (ZFP36) gene has been identified as the most promising genetic target for the MS-based mean fold expression differences and on biological plausibility. 2 out of 5 identified ZFP36 gene polymorphisms have been genotyped in a cohort of 698 obese subjects. The minor allele of these polymorphisms was associated with a lower body weight in women (rs251864; P≤0.01) and glucose level in men (c.1564_1565delTT; P<0.05). The haplogenotype was associated with plasma LDL-cholesterol levels in men and women (P≤0.02), and weight in women (P≤0.05). The haplogenotype was also associated with omental adipose tissue ZFP36 mRNA levels (n=83 women; P=0.02), and explained 10.1% of its variance.

Conclusion

These results suggest that converging genomics is helpful to prioritize MS-related candidate genes and that ZFP36 is a promising candidate gene for obesity-associated metabolic complications.

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Abbreviations

MS:

metabolic syndrome

CVD:

cardiovascular disease

ZFP36:

zinc finger protein 36

NCEP-ATPIII:

National Cholesterol Education Program -Adult Treatment Panel III

QTLs:

quantitative trait loci

AT:

adipose tissue

mRNA:

messenger ribonucleic acid

RT-PCR:

reverse transcriptase polymerase chain reaction

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Authors and Affiliations

  1. Lipid Research Center, Laval University, Québec, Canada

    Luigi Bouchard & Marie-Claude Vohl PhD

  2. Nutraceuticals and Functional Foods Institute, Laval University, Québec, Canada

    Luigi Bouchard, André Tchernof & Marie-Claude Vohl PhD

  3. Department of Food Science and Nutrition, Laval University, Québec, Canada

    Luigi Bouchard, André Tchernof & Marie-Claude Vohl PhD

  4. Molecular Endocrinology and Oncology Research Center, Laval University, Québec, Canada

    André Tchernof

  5. Department of Anatomy and Physiology and Laval Hospital Research Center, Laval University, Québec, Canada

    Yves Deshaies

  6. Department of Surgery, Medicine Faculty, Laval University, Québec, Canada

    Simon Marceau, Odette Lescelleur & Simon Biron

  7. Lipid research Center, 2705 Laurier Blvd, (TR93), Québec City, PQ, Canada, G1V 4G2

    Marie-Claude Vohl PhD

Authors
  1. Luigi Bouchard
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  2. André Tchernof
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  3. Yves Deshaies
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  5. Odette Lescelleur
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  7. Marie-Claude Vohl PhD
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Correspondence to Marie-Claude Vohl PhD.

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Bouchard, L., Tchernof, A., Deshaies, Y. et al. ZFP36: a Promising Candidate Gene for Obesity-Related Metabolic Complications Identified by Converging Genomics. OBES SURG 17, 372–382 (2007). https://doi.org/10.1007/s11695-007-9067-5

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  • DOI: https://doi.org/10.1007/s11695-007-9067-5

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