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Association between tumour necrosis factor-alpha G-308A polymorphism and risk of nephropathy in obese Chinese type 2 diabetic patients.
Nephrol Dial Transplant. 2005 Dec; 20(12):2733-8.ND

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 > or =150 micromol/L and/or mean ACR > or =25 mg/mmol. Obesity was defined as body mass index > or =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) microg/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.

Authors+Show Affiliations

Divison of Endocrinology, Department of Medicine & Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16141456

Citation

Wang, Ying, et al. "Association Between Tumour Necrosis Factor-alpha G-308A Polymorphism and Risk of Nephropathy in Obese Chinese Type 2 Diabetic Patients." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 20, no. 12, 2005, pp. 2733-8.
Wang Y, Ng MC, So WY, et al. Association between tumour necrosis factor-alpha G-308A polymorphism and risk of nephropathy in obese Chinese type 2 diabetic patients. Nephrol Dial Transplant. 2005;20(12):2733-8.
Wang, Y., Ng, M. C., So, W. Y., Ma, R., Ko, G. T., Tong, P. C., & Chan, J. C. (2005). Association between tumour necrosis factor-alpha G-308A polymorphism and risk of nephropathy in obese Chinese type 2 diabetic patients. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 20(12), 2733-8.
Wang Y, et al. Association Between Tumour Necrosis Factor-alpha G-308A Polymorphism and Risk of Nephropathy in Obese Chinese Type 2 Diabetic Patients. Nephrol Dial Transplant. 2005;20(12):2733-8. PubMed PMID: 16141456.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association between tumour necrosis factor-alpha G-308A polymorphism and risk of nephropathy in obese Chinese type 2 diabetic patients. AU - Wang,Ying, AU - Ng,Maggie C Y, AU - So,Wing-Yee, AU - Ma,Ronald, AU - Ko,Gary T C, AU - Tong,Peter C Y, AU - Chan,Juliana C N, Y1 - 2005/09/02/ PY - 2005/9/6/pubmed PY - 2006/2/16/medline PY - 2005/9/6/entrez SP - 2733 EP - 8 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol Dial Transplant VL - 20 IS - 12 N2 - 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 > or =150 micromol/L and/or mean ACR > or =25 mg/mmol. Obesity was defined as body mass index > or =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) microg/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. SN - 0931-0509 UR - https://www.unboundmedicine.com/medline/citation/16141456/Association_between_tumour_necrosis_factor_alpha_G_308A_polymorphism_and_risk_of_nephropathy_in_obese_Chinese_type_2_diabetic_patients_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfi101 DB - PRIME DP - Unbound Medicine ER -