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

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

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
Further Information

Publication History

received 02.10.2009 first decision 02.10.2009

accepted 25.11.2009

Publication Date:
05 February 2010 (online)

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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

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Correspondence

Dr. Y.-J. Lee

Director

Lee's Endocrinologic Clinic

No. 130 Min-Tzu Rd

90000 Pingtung

Taiwan

Phone: +8868-7668901

Fax: +8868-7668902

Email: t3275@ms25.hinet.net

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