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NDT Advance Access published online on September 2, 2005
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfi101
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received December 21, 2004
Accepted August 2, 2005

Original Articles

Association between tumor necrosis factor-{alpha} G-308A polymorphism and risk of nephropathy in obese Chinese type 2 diabetic patients

Ying Wang 1, Maggie C. Y. Ng 1, Wing-Yee So 1*, Ronald Ma 1, Gary T. C. Ko 1, Peter C. Y. Tong 1, and Juliana C. N. Chan 1

1 From the Division of Endocrinology, Department of Medicine & Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR

* To whom correspondence should be addressed.
Wing-Yee So, E-mail: wingyeeso{at}cuhk.edu.hk



  Abstract

Background. The G-308A polymorphism in the promoter region of the tumor necrosis factor alpha (TNF-{alpha}) gene has been reported to be associated with insulin resistance and obesity, both of which may increase the risk of diabetic nephropathy. We hypothesized that this polymorphism might interact with obesity to affect development of diabetic nephropathy.

Methods. A consecutive cohort of 1281 Chinese type 2 diabetic patients was enrolled for analysis. Genotyping of TNF-{alpha} G-308A polymorphism was performed using a PCR-based RFLP method with NcoI digestion. The mean value of the albumin creatinine ratio (ACR) of a random spot urine sample and a timed urinary collection was used to determine albuminuric status. Diabetic nephropathy was defined as serum creatinine ≥150 µmol/L and/or mean ACR ≥25 mg/mmol. Obesity was defined as body mass index ≥25 kg/m2 using Asian criteria.

Results. The G-308A polymorphism was not associated with either obesity or nephropathy. Clinical characteristics were similar between GG and GA/AA genotype carriers. Amongst the obese patients, GG genotype carriers had a higher median (interquartile range) urinary ACR [3.16 (0.70, 59.10) vs 1.28 (0.48, 12.28) mg/mmol; p = 0.01] and albumin excretion rate [38.7 (12.1, 620.3) vs 21.4 (8.9, 224.0) µg/min, p = 0.03] than GA/AA carriers. On multiple logistic regression analysis, compared with non-obese GA/AA carriers, obese subjects with the GG genotype had a 2.5-fold increased risk (95% CI: 1.04-6.03; P = 0.04) of nephropathy after adjustment for confounding factors. Other independent factors for diabetic nephropathy included male sex, systolic blood pressure, triglycerides (logarithmically transformed value), and the presence of cardiovascular and microvascular complications.

Conclusion. Our findings suggest that the GG genotype of TNF-{alpha} G-308A polymorphism or a genetic variant in close linkage disequilibrium may interact with obesity to increase the risk of nephropathy in Chinese Type 2 diabetic patients. Apart from the need for replication of these results, functional studies are required to clarify its significance.

Keywords: chinese type 2 diabetes; diabetic nephropathy; obesity; tnf-{alpha}.
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