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Exp Clin Endocrinol Diabetes. 2010 Jun;118(6):346-52. doi: 10.1055/s-0029-1243604. Epub 2010 Feb 5.

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.

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  • 1Division of Cardiology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 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-gamma and PPAR-alpha 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/m (2) 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-beta 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.

(c) J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart, New York.

PMID:
20140850
[PubMed - indexed for MEDLINE]
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