RESEARCH ARTICLE

Insulin receptor substrate-2 gene variants in subjects with metabolic syndrome: Association with plasma monounsaturated and n-3 polyunsaturated fatty acid levels and insulin resistance

  1. Pablo Perez-Martinez1,†,
  2. Javier Delgado-Lista1,†,
  3. Antonio Garcia-Rios1,
  4. Audrey C. Tierney2,
  5. Hanne L. Gulseth3,
  6. Christine M. Williams4,
  7. Brita Karlström5,
  8. Beata Kieć-Wilk6,
  9. Ellen E. Blaak7,
  10. Olfa Helal8,
  11. Wim H. M. Saris7,
  12. Catherine Defoort8,
  13. Christian A. Drevon9,
  14. Julie A. Lovegrove4,
  15. Aldona Dembinska-Kieć6,
  16. Ulf Riserus6,
  17. Helen M. Roche2,
  18. Jose Lopez-Miranda1,*

Article first published online: 7 DEC 2011

DOI: 10.1002/mnfr.201100504

Issue

Molecular Nutrition & Food Research

Molecular Nutrition & Food Research

Special Issue: Carotenoids in Nutrition and Health - Developments and Future Trends

Volume 56, Issue 2, pages 309–315, February 2012

Additional Information

How to Cite

Perez-Martinez, P., Delgado-Lista, J., Garcia-Rios, A., Tierney, A. C., Gulseth, H. L., Williams, C. M., Karlström, B., Kieć-Wilk, B., Blaak, E. E., Helal, O., Saris, W. H. M., Defoort, C., Drevon, C. A., Lovegrove, J. A., Dembinska-Kieć, A., Riserus, U., Roche, H. M. and Lopez-Miranda, J. (2012), Insulin receptor substrate-2 gene variants in subjects with metabolic syndrome: Association with plasma monounsaturated and n-3 polyunsaturated fatty acid levels and insulin resistance. Mol. Nutr. Food Res., 56: 309–315. doi: 10.1002/mnfr.201100504

Author Information

  1. 1

    Lipid and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Cordoba, and CIBER Fisiopatologia Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos, Cordoba, Spain

  2. 2

    Nutrigenomics Research Group, UCD School of Public Health and Population Science, UCD Conway Institute, University College Dublin, Dublin, Ireland

  3. 3

    Department of Endocrinology, Oslo University Hospital, Oslo, Norway

  4. 4

    Department of Food and Nutritional Sciences and the Institute for Cardiovascular and Metabolic Research, University of Reading, Reading, Berkshire, UK

  5. 5

    Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden

  6. 6

    Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland

  7. 7

    Department of Human Biology, NUTRIM, School for Nutrition, Toxicology and Metabolism, Maastricht, The Netherlands

  8. 8

    INSERM, Lipid Nutrients and Prevention of Metabolic Diseases; INRA, 1260, Université de la Méditerranée, Marseille, France

  9. 9

    Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway

  1. †

    These authors contributed equally to this work.

*Correspondence: Dr. Jose Lopez-Miranda, Reina Sofia University Hospital, Lipids and Atherosclerosis Research Unit. Avda. Menéndez Pidal, s/n. 14004 Córdoba, Spain
E-mail:jlopezmir@uco.es
Fax: +34-957218250

Publication History

  1. Issue published online: 14 MAR 2012
  2. Article first published online: 7 DEC 2011
  3. Manuscript Accepted: 22 SEP 2011
  4. Manuscript Revised: 1 SEP 2011
  5. Manuscript Received: 25 JUL 2011

Funded by

  • European community (LIPGENE European Integrated Project-505944)
  • Spanish Ministry of Science and Innovation. Grant Numbers: AGL2006-01979/ALI, AGL2009-12270, PI10/01041
  • Consejería de Economía, Innovación y Ciencia, Proyectos de Investigación de Excelencia, Junta de Andalucía. Grant Number: P06-CTS-01425
  • Consejería de Salud
  • Junta de Andalucía. Grant Numbers: 07/43, PI 0193/09, PI-0252/2009, PI-0058-2010
  • Johan Throne Holst Foundation for Nutrition Research and Freia Medical Research Fund, Norway
  • Centro de Excelencia Investigadora en Aceite de Oliva y Salud (CEAS)
  • Science Foundation Ireland Principal Investigator Programme. Grant Number: 06/IM.1/B105
  • ISCIII (Programa Río-Hortega)

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Keywords:

  • Fatty acids;
  • Metabolic syndrome;
  • Nutrigenomics;
  • n-3 PUFA;
  • Polymorphism

Scope

Several insulin receptor substrate-2 (IRS-2) polymorphisms have been studied in relation to insulin resistance and type 2 diabetes. To examine whether the genetic variability at the IRS-2 gene locus was associated with the degree of insulin resistance and plasma fatty acid levels in metabolic syndrome (MetS) subjects.

Methods and results

Insulin sensitivity, insulin secretion, glucose effectiveness, plasma fatty acid composition and three IRS-2 tag-single nucleotide polymorphisms (SNPs) were determined in 452 MetS subjects. Among subjects with the lowest level of monounsaturated (MUFA) (below the median), the rs2289046 A/A genotype was associated with lower glucose effectiveness (p<0.038), higher fasting insulin concentrations (p<0.028) and higher HOMA IR (p<0.038) as compared to subjects carrying the minor G-allele (A/G and G/G). In contrast, among subjects with the highest level of MUFA (above the median), the A/A genotype was associated with lower fasting insulin concentrations and HOMA-IR, whereas individuals carrying the G allele and with the highest level of ω-3 polyunsaturated fatty acids (above the median) showed lower fasting insulin (p<0.01) and HOMA-IR (p<0.02) as compared with A/A subjects.

Conclusion

The rs2289046 polymorphism at the IRS2 gene locus may influence insulin sensitivity by interacting with certain plasma fatty acids in MetS subjects.

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