This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barbieri, M. Articles by Paolisso, G. Search for Related Content PubMed PubMed Citation Articles by Barbieri, M. Articles by Paolisso, G.

LL-Paraoxonase Genotype Is Associated with a More Severe Degree of Homeostasis Model Assessment IR in Healthy Subjects

Department of Geriatric Medicine and Metabolic Diseases (M.Ba., R.M., E.R., D.G., G.P.), Second University of Naples, I-80138 Naples, Italy; and Department of Experimental Pathology (M.Bo., C.F.), University of Bologna, 40126 Bologna, Italy

Address all correspondence and requests for reprints to: Prof. Giuseppe Paolisso, IV Divisione di Medicina Interna e Malattie dell’Invecchiamento, Cattedra di Geriatria, Department of Geriatric Medicine and Metabolic Diseases, Piazza Miraglia 2, I-80138 Napoli, Italy. E-mail: giuseppe.paolisso{at}unina2.it

The LL genotype among subjects with paraoxonase (PON) polymorphism Met-Leu 54 has been shown to be associated with elevated risk of coronary heart disease. Indeed, insulin resistance (IR) is a well known cardiovascular risk factor that is likely attributable to a genetic background, lifestyle, and environmental factors such oxidative stress. Because subjects sharing the LL genotype have a more elevated degree of oxidative stress, one cannot rule out that in those subjects a more severe degree of IR can occur. Thus, the possible relationship between PON gene polymorphism and degree of IR was investigated.

In 213 healthy subjects, the degree of IR was assessed by the homeostasis model assessment, and the Met-Leu 54 PON polymorphism was detected.

The frequency was 0.366 for the LL genotype, 0.469 for the LM genotype, and 0.164 for the MM genotype. Comparing the three genotype groups, LL genotype had the more severe degree of IR, compared with LM (P < 0.01) and MM (P < 0.01) genotypes. No difference between LM and MM genotypes was found (P = 0.49). Subjects carrying the LL genotype were associated with the IR syndrome picture more than individuals carrying the M allele because they were more overweight and had the highest levels of triglycerides and blood pressure and the lowest values of plasma high-density lipoprotein cholesterol. In a multivariate stepwise regression analysis, LL genotype was a significant predictor of IR, independent of age, sex, body mass index, fasting plasma triglycerides, and high-density lipoprotein cholesterol (P < 0.001).

In conclusion, the presence of LL PON genotype is associated with a more severe degree of IR. Thus, IR might be the possible missing link between Met-Leu 54 PON polymorphism and the increased cardiovascular risk.

Abbreviations: BMI, Body mass index; CV, coefficient of variation; HDL, high-density lipoprotein; HOMA, homeostasis model assessment; IR, insulin resistance; LDL, low-density lipoprotein; PON, paraoxonase.

This article has been cited by other articles:

				J. L. San Millan, M. Corton, G. Villuendas, J. Sancho, B. Peral, and H. F. Escobar-Morreale Association of the Polycystic Ovary Syndrome with Genomic Variants Related to Insulin Resistance, Type 2 Diabetes Mellitus, and Obesity J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2640 - 2646. [Abstract] [Full Text] [PDF]

				M. Senti, M. Tomas, M. Fito, T. Weinbrenner, M.-I. Covas, J. Sala, R. Masia, and J. Marrugat Antioxidant Paraoxonase 1 Activity in the Metabolic Syndrome J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5422 - 5426. [Abstract] [Full Text] [PDF]