|
 |
|
|||||||
|
|||||||||
© 2001 by the American Diabetes Association, Inc.
Evidence for Gene-Nutrient Interaction at the PPAR
Locus
1 Public Health and Primary Care and
2 Medicine and Clinical Biochemistry, University of Cambridge, Cambridge, U.K.
The importance of the nuclear receptor peroxisome proliferator–activated receptor-
(PPAR) in regulating insulin resistance and blood pressure has been demonstrated in families with loss of function mutations. Gain of function mutations has been associated with severe obesity. However, previous population studies of the common variant Pro12Ala have produced conflicting results. As it is likely that the natural ligands for this receptor may include fatty acids, we hypothesized that the effect of this common variant may be altered by the character of the diet, particularly the ratio of dietary polyunsaturated fat to saturated fat (P:S ratio). We studied 592 nondiabetic participants in an ongoing population-based cohort study who were genotyped for the Pro12Ala polymorphism in the PPAR 2 isoform. As the Ala homozygotes were uncommon (2.0%), all analyses were conducted comparing Pro homozygotes (79.1%) to Ala allele carriers. There was no difference in fasting insulin concentration or BMI between Ala allele carriers and Pro homozygotes. The fasting insulin concentration was negatively associated with the P:S ratio (P = 0.0119) after adjustment for age and sex, and a strong interaction was evident between the P:S ratio and the Pro12Ala polymorphism for both BMI (P = 0.0038) and fasting insulin (P = 0.0097). The data suggest that when the dietary P:S ratio is low, the BMI in Ala carriers is greater than that in Pro homozygotes, but when the dietary ratio is high, the opposite is seen. This gene-nutrient interaction emphasizes the difficulty of examining the effect of common polymorphisms in the absence of data on nongenetic exposures, and may explain the heterogeneity of findings in previous studies.
Abbreviations:
PCR, polymerase chain reaction; PPAR, peroxisome proliferator–activated receptor-; P:S ratio; polyunsaturated:saturated fat ratio
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. E Cecil, C. N. Palmer, B. Fischer, P. Watt, D. J Wallis, I. Murrie, and M. M Hetherington Variants of the peroxisome proliferator-activated receptor {gamma}- and {beta}-adrenergic receptor genes are associated with measures of compensatory eating behaviors in young children Am. J. Clinical Nutrition, July 1, 2007; 86(1): 167 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Vaccaro, E. Lapice, A. Monticelli, M. Giacchetti, I. Castaldo, R. Galasso, M. Pinelli, G. Donnarumma, A. A. Rivellese, S. Cocozza, et al. Pro12Ala Polymorphism of the PPAR{gamma}2 Locus Modulates the Relationship Between Energy Intake and Body Weight in Type 2 Diabetic Patients Diabetes Care, May 1, 2007; 30(5): 1156 - 1161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tonjes, M. Scholz, M. Loeffler, and M. Stumvoll Association of Pro12Ala Polymorphism in Peroxisome Proliferator-Activated Receptor {gamma} With Pre-Diabetic Phenotypes: Meta-analysis of 57 studies on nondiabetic individuals. Diabetes Care, November 1, 2006; 29(11): 2489 - 2497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Soriguer, S. Morcillo, F. Cardona, G. Rojo-Martinez, M. de la Cruz Almaraz, M. de la Soledad Ruiz de Adana, G. Olveira, F. Tinahones, and I. Esteva Pro12Ala Polymorphism of the PPARG2 Gene Is Associated with Type 2 Diabetes Mellitus and Peripheral Insulin Sensitivity in a Population with a High Intake of Oleic Acid J. Nutr., September 1, 2006; 136(9): 2325 - 2330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Corella, L. Qi, E. S. Tai, M. Deurenberg-Yap, C. E. Tan, S. K. Chew, and J. M. Ordovas Perilipin Gene Variation Determines Higher Susceptibility to Insulin Resistance in Asian Women When Consuming a High-Saturated Fat, Low-Carbohydrate Diet. Diabetes Care, June 1, 2006; 29(6): 1313 - 1319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Al-Zahrani, M. S. Sandhu, R. N. Luben, D. Thompson, C. Baynes, K. A. Pooley, C. Luccarini, H. Munday, B. Perkins, P. Smith, et al. IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer Hum. Mol. Genet., January 1, 2006; 15(1): 1 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Sookoian, S I Garcia, P I Porto, G Dieuzeide, C D Gonzalez, and C J Pirola Peroxisome proliferator-activated receptor gamma and its coactivator-1 alpha may be associated with features of the metabolic syndrome in adolescents J. Mol. Endocrinol., October 1, 2005; 35(2): 373 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Mutch, W. Wahli, and G. Williamson Nutrigenomics and nutrigenetics: the emerging faces of nutrition FASEB J, October 1, 2005; 19(12): 1602 - 1616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Paracchini, P. Pedotti, and E. Taioli Genetics of Leptin and Obesity: A HuGE Review Am. J. Epidemiol., July 15, 2005; 162(2): 101 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Stefan, S. Schafer, F. Machicao, J. Machann, F. Schick, C. D. Claussen, M. Stumvoll, H.-U. Haring, and A. Fritsche Liver Fat and Insulin Resistance Are Independently Associated with the -514C>T Polymorphism of the Hepatic Lipase Gene J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4238 - 4243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Ehrich, T. Hrbek, J. P. Kenney-Hunt, L. S. Pletscher, B. Wang, C. F. Semenkovich, and J. M. Cheverud Fine-Mapping Gene-by-Diet Interactions on Chromosome 13 in a LG/J x SM/J Murine Model of Obesity Diabetes, June 1, 2005; 54(6): 1863 - 1872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E.C. Tok, A. Aktas, D. Ertunc, E.M. Erdal, and S. Dilek Evaluation of glucose metabolism and reproductive hormones in polycystic ovary syndrome on the basis of peroxisome proliferator-activated receptor (PPAR)-{gamma}2 Pro12Ala genotype Hum. Reprod., June 1, 2005; 20(6): 1590 - 1595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K M Eny, A El-Sohemy, M C Cornelis, Y-K Sung, and S-C Bae Catalase and PPARg2 genotype and risk of systemic lupus erythematosus in Koreans Lupus, May 1, 2005; 14(5): 351 - 355. [Abstract] [PDF]
|
|
|
|
|
|
R. E. Pisabarro, C. Sanguinetti, M. Stoll, and D. Prendez High Incidence of Type 2 Diabetes in Peroxisome Proliferator-Activated Receptor {gamma}2 Pro12Ala Carriers Exposed to a High Chronic Intake of Trans Fatty Acids and Saturated Fatty Acids Diabetes Care, September 1, 2004; 27(9): 2251 - 2252. [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Tai, D. Corella, M. Deurenberg-Yap, X. Adiconis, S. K. Chew, C. E. Tan, and J. M. Ordovas Differential effects of the C1431T and Pro12Ala PPAR{gamma} gene variants on plasma lipids and diabetes risk in an Asian population J. Lipid Res., April 1, 2004; 45(4): 674 - 685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Memisoglu, F. B. Hu, S. E. Hankinson, J. E. Manson, I. De Vivo, W. C. Willett, and D. J. Hunter Interaction between a peroxisome proliferator-activated receptor {gamma} gene polymorphism and dietary fat intake in relation to body mass Hum. Mol. Genet., November 15, 2003; 12(22): 2923 - 2929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Greenfield, K. Samaras, A. B. Jenkins, P. J. Kelly, T. D. Spector, and L. V. Campbell Moderate Alcohol Consumption, Dietary Fat Composition, and Abdominal Obesity in Women: Evidence for Gene-Environment Interaction J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5381 - 5386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Masud and S Ye Effect of the peroxisome proliferator activated receptor-{gamma} gene Pro12Ala variant on body mass index: a meta-analysis J. Med. Genet., October 1, 2003; 40(10): 773 - 780. [Full Text] [PDF]
|
|
|
|
|
|
J. A. Martinez, M. S. Corbalan, A. Sanchez-Villegas, L. Forga, A. Marti, and M. A. Martinez-Gonzalez Obesity Risk Is Associated with Carbohydrate Intake in Women Carrying the Gln27Glu {beta}2-Adrenoceptor Polymorphism J. Nutr., August 1, 2003; 133(8): 2549 - 2554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gurnell, D. B. Savage, V. K. K. Chatterjee, and S. O'Rahilly The Metabolic Syndrome: Peroxisome Proliferator-Activated Receptor {gamma} and Its Therapeutic Modulation J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2412 - 2421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.H. L. Kao, J. Coresh, A. R. Shuldiner, E. Boerwinkle, M. S. Bray, and F. L. Brancati Pro12Ala of the Peroxisome Proliferator-Activated Receptor-{gamma}2 Gene Is Associated With Lower Serum Insulin Levels in Nonobese African Americans: The Atherosclerosis Risk in Communities Study Diabetes, June 1, 2003; 52(6): 1568 - 1572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kolehmainen, M. I. J. Uusitupa, E. Alhava, M. Laakso, and H. Vidal Effect of the Pro12Ala Polymorphism in the Peroxisome Proliferator-Activated Receptor (PPAR) {gamma}2 Gene on the Expression of PPAR{gamma} Target Genes in Adipose Tissue of Massively Obese Subjects J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1717 - 1722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bluher, G. Lubben, and R. Paschke Analysis of the Relationship Between the Pro12Ala Variant in the PPAR-{gamma}2 Gene and the Response Rate to Therapy With Pioglitazone in Patients With Type 2 Diabetes Diabetes Care, March 1, 2003; 26(3): 825 - 831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Lovejoy, S. R. Smith, C. M. Champagne, M. M. Most, M. Lefevre, J. P. DeLany, Y. M. Denkins, J. C. Rood, J. Veldhuis, and G. A. Bray Effects of Diets Enriched in Saturated (Palmitic), Monounsaturated (Oleic), or trans (Elaidic) Fatty Acids on Insulin Sensitivity and Substrate Oxidation in Healthy Adults Diabetes Care, August 1, 2002; 25(8): 1283 - 1288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Stumvoll and H. Haring The Peroxisome Proliferator-Activated Receptor-{gamma}2 Pro12Ala Polymorphism Diabetes, August 1, 2002; 51(8): 2341 - 2347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. I. Lindi, M. I.J. Uusitupa, J. Lindstrom, A. Louheranta, J. G. Eriksson, T. T. Valle, H. Hamalainen, P. Ilanne-Parikka, S. Keinanen-Kiukaanniemi, M. Laakso, et al. Association of the Pro12Ala Polymorphism in the PPAR-{gamma}2 Gene With 3-Year Incidence of Type 2 Diabetes and Body Weight Change in the Finnish Diabetes Prevention Study Diabetes, August 1, 2002; 51(8): 2581 - 2586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Eriksson, V. Lindi, M. Uusitupa, T. J. Forsen, M. Laakso, C. Osmond, and D. J.P. Barker The Effects of the Pro12Ala Polymorphism of the Peroxisome Proliferator-Activated Receptor-{gamma}2 Gene on Insulin Sensitivity and Insulin Metabolism Interact With Size at Birth Diabetes, July 1, 2002; 51(7): 2321 - 2324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Elbein Perspective: The Search for Genes for Type 2 Diabetes in the Post-Genome Era Endocrinology, June 1, 2002; 143(6): 2012 - 2018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Dobbins, L. S. Szczepaniak, J. Myhill, Y. Tamura, H. Uchino, A. Giacca, and J. D. McGarry The Composition of Dietary Fat Directly Influences Glucose-Stimulated Insulin Secretion in Rats Diabetes, June 1, 2002; 51(6): 1825 - 1833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Meirhaeghe, J.'a. Luan, P. Selberg-Franks, S. Hennings, J. Mitchell, D. Halsall, S. O'Rahilly, and N. J. Wareham The Effect of the Gly16Arg Polymorphism of the {beta}2-Adrenergic Receptor Gene on Plasma Free Fatty Acid Levels Is Modulated by Physical Activity J. Clin. Endocrinol. Metab., December 1, 2001; 86(12): 5881 - 5887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J.M. Feskens Can Diabetes Be Prevented by Vegetable Fat? Diabetes Care, September 1, 2001; 24(9): 1517 - 1518. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |