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.
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 diabeticpatients was enrolled for analysis. Genotyping of TNF-alphaG-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 obesepatients, 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-alphaG-308A polymorphism or a genetic variant in close linkage disequilibrium may interact with obesity to increase the risk of nephropathy in Chinese Type 2 diabeticpatients. Apart from the need for replication of these results, functional studies are required to clarify its significance.
Authors: Amina Nadeem; Sadaf Mumtaz; Abdul Khaliq Naveed; Muhammad Aslam; Arif Siddiqui; Ghulam Mustafa Lodhi; Tausif Ahmad Journal: World J Diabetes Date: 2015-05-15
Authors: Diana I Vázquez-Huerta; Bertha A Alvarez-Rodríguez; Jorge F Topete-Reyes; José F Muñoz-Valle; Renato Parra-Michel; Francisco Fuentes-Ramírez; María A Salazar-López; Yeminia Valle; Zyanya Reyes-Castillo; A Cruz-González; Lorena M Brennan-Bourdon; Norma Torres-Carrillo Journal: Int J Clin Exp Med Date: 2014-08-15
Authors: Luz E Chavarria-Buenrostro; Jorge Hernandez-Bello; Jose F Muñoz-Valle; Jose Macias-Barragan; Liliana B Hernandez-Carrillo; Jorge F Topete-Reyes; Renato Parra-Michel; Maria G Ramirez-Dueñas; Pedro E Sanchez-Hernandez; Ana L Pereira-Suarez; Eden Oceguera-Contreras; Margarita Montoya-Buelna Journal: J Clin Lab Anal Date: 2018-10-21 Impact factor: 2.352
Authors: C K Wong; A W Y Ho; P C Y Tong; C Y Yeung; A P S Kong; S W M Lun; J C N Chan; C W K Lam Journal: Clin Exp Immunol Date: 2007-04-11 Impact factor: 4.330