Perilipin Gene Variation Determines Higher Susceptibility to Insulin Resistance in Asian Women When Consuming a High–Saturated Fat, Low-Carbohydrate Diet

  1. Dolores Corella, PHD12,
  2. Lu Qi, PHD1,
  3. E. Shyong Tai, MD3,
  4. Mabel Deurenberg-Yap, PHD4,
  5. Chee Eng Tan, MD3,
  6. Suok Kai Chew, MD5 and
  7. Jose M. Ordovas, PHD1
  1. 1Nutrition and Genomics Laboratory, Jean Mayer–U.S. Department of Agriculture Human Nutrition Center on Aging at Tufts University, Boston, Massachusetts
  2. 2Genetic and Molecular Epidemiology Unit, Valencia University, Valencia, Spain
  3. 3Department of Endocrinology, Singapore General Hospital, Singapore
  4. 4Research and Information Management Division, Health Promotion Board, Singapore
  5. 5Epidemiology and Disease Control Division, Ministry of Health, Singapore
  1. Address correspondence and reprint requests to Jose M. Ordovas, Nutrition and Genomics Laboratory, JM-USDA-HNRCA at Tufts University, 711 Washington St., Boston, MA 02111. E-mail:jose.ordovas{at}tufts.edu

Abstract

OBJECTIVE—To investigate the association between genetic variation in the adipocyte protein perilipin (PLIN) and insulin resistance in an Asian population as well as to examine their modulation by macronutrient intake.

RESEARCH DESIGN AND METHODS—A nationally representative sample (Chinese, Malays, and Indians) was selected in the Singapore National Health Survey following the World Health Organization–recommended model for field surveys of diabetes. A total of 1,909 men and 2,198 women (aged 18–69 years) were studied. Genetic (PLIN 11482G→A and 14995A→T), lifestyle, clinical, and biochemical data were obtained. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate insulin resistance. Diet was measured by a validated food frequency questionnaire in one of every two subjects.

RESULTS—We did not find a significant between-genotype difference in insulin resistance measures. However, in women we found statistically significant gene-diet interactions (recessive model) between PLIN 11482G→A/14995A→T polymorphisms (in high linkage disequilibrium) and saturated fatty acids (SFAs; P = 0.003/0.005) and carbohydrate (P = 0.004/0.012) in determining HOMA-IR. These interactions were in opposite directions and were more significant for 11482G→A, considered the tag polymorphism. Thus, women in the highest SFA tertile (11.8–19%) had higher HOMA-IR (48% increase; P trend = 0.006) than women in the lowest (3.1–9.4%) only if they were homozygotes for the PLIN minor allele. Conversely, HOMA-IR decreased (−24%; P trend = 0.046) as carbohydrate intake increased. These effects were stronger when SFAs and carbohydrate were combined as an SFA-to-carbohydrate ratio. Moreover, this gene-diet interaction was homogeneously found across the three ethnic groups.

CONCLUSIONSPLIN 11482G→A/14995A→T polymorphisms modulate the association between SFAs/carbohydrate in diet and insulin resistance in Asian women.

Footnotes

  • D.C. and L.Q. are joint first authors of this article.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted March 11, 2006.
    • Received January 7, 2006.
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