Genetic Variation in the G-50T Polymorphism of the Cytochrome P450 Epoxygenase CYP2J2 Gene and the Risk of Younger Onset Type 2 Diabetes among Chinese Population: Potential Interaction with Body Mass Index and Family History

C.-P. Wang; W.-C. Hung; T.-H. Yu; C.-A. Chiu; L.-F. Lu; F.-M. Chung; C.-H. Hung; S.-J. Shin; H.-J. Chen; Y.-J. Lee

doi:10.1055/s-0029-1243604

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2010; 118(6): 346-352
DOI: 10.1055/s-0029-1243604

Article

Genetic Variation in the G-50T Polymorphism of the Cytochrome P450 Epoxygenase CYP2J2 Gene and the Risk of Younger Onset Type 2 Diabetes among Chinese Population: Potential Interaction with Body Mass Index and Family History

C.-P. Wang¹ ^, ⁴ , W.-C. Hung¹ , T.-H. Yu¹ , C.-A. Chiu¹ , L.-F. Lu² , F.-M. Chung¹ , C.-H. Hung⁴ , S.-J. Shin⁵ , H.-J. Chen³ , Y.-J. Lee⁶

¹Division of Cardiology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
²Division of Cardiac Surgery, Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
³Division of Neurology, Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
⁴Department of Medical Nutrition, Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan
⁵Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
⁶Lee's Endocrinologic Clinic, Pingtung, Taiwan

Abstract

Background: Cytochrome P450 (CYP) 2J2 is a regulatory enzyme in the biosynthesis of biologically active cis-epoxyeicosatrienoic acids (EETs). EETs have been suggested to modulate PPAR-γ and PPAR-α transcription activity and play a role in stimulus-secretion coupling in pancreatic beta cells. Genetic abnormalities in the expression of CYP2J enzymes may play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). Our objective was to investigate CYP2J2 G-50T polymorphism (rs890293) in association with insulin resistance markers and T2DM in a Chinese population.

Methods: A total of 1 747 Chinese T2DM patients and 994 non-diabetic subjects were studied. The CYP2J2 G-50T polymorphism was determined by a restriction fragment-length polymorphism polymerase chain reaction.

Results: Neither the CYP2J2 genotype distribution nor allele frequency differed between the control subjects and the T2DM patients. However, among diabetics, subjects with a younger age at diagnosis (AAD; <40 years) had significantly higher T variant frequency than those with an AAD≥40 years. When diabetic patients were stratified by their AAD in 10-year intervals, the trend was significantly linear among age grades. A significant interaction between the CYP2J2 T variant and younger onset diabetic subjects with positive family diabetes history, and BMI≥27 kg/m² were observed to have the highest risk of diabetes and younger onset diabetics with the T variant had higher homeostasis model assessment estimate of insulin resistance (HOMA-IR) and HOMA-β values than their GG genotype counterparts. Plasma concentrations of stable EET metabolites were significantly lower in individuals with the G-50T SNP in younger onset diabetics.

Conclusion: These data suggest that age of onset, family history, and obesity may modify the association between the CYP2J2 G-50T polymorphism and T2DM risk. CYP2J2 G-50T polymorphism may contribute to the pathogenesis of T2DM, partially by effects on insulin resistance, in patients with younger onset T2DM.

Key words

younger onset type 2 diabetes - CYP2J2 G-50T polymorphism - obesity - family history - insulin resistance

Full Text

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Dr. Y.-J. Lee

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