Abstract
The aim of the present study was to evaluate the relationship of the manganese superoxide dismutase (MnSOD) Val16Ala (V16A) polymorphism with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in Chinese patients, a case-control study was performed. This case-control study included 172 non-diabetic (non-DM) subjects and 257 T2DM patients with or without DN. Among T2DM patients, 154 had DN [albumin excretion rate (AER) ≥ 30 mg/24 h] and 103 did not (AER < 30 mg/24 h), but the latter with known diabetes duration ≥10 years. The DN patients were further divided into groups with microalbuminuria (DN-1; n = 92; 300 > AER ≥ 30 mg/24 h) and overt albuminuria nephropathy (DN-2; n = 62; AER ≥ 300 mg/24 h). PCR-restriction fragment length polymorphism (RFLP) was used to detect genotypes of the V16A polymorphism for all subjects. The genotypic distributions of the V16A polymorphism in non-DM and T2DM subjects were in Hardy–Weinberg equilibrium and Ala allelic frequencies did not differ (11.9% vs. 9.1%; P > 0.05). The AA+VA genotypic frequencies of DN patients were significantly lower than those of non-DN patients (11.6% vs. 24.3%; P = 0.008). Multiple logistic regression analysis revealed that except for HbA1C, triglyceride, and BMI, which were high risk factors for the development of DN, the AA+VA genotype of the MnSOD-V16A polymorphism was an independent protective factor from the development of DN (odds ratio = 0.42; 95% CI = 0.18–0.95; P = 0.037) in T2DM patients. Our results suggested that the MnSOD-V16A polymorphism is associated with decreased risk of diabetic nephropathy in Chinese patients with type 2 diabetes.
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References
Freedman BI, Bostrom M, Daeihagh P et al (2007) Genetic factors in diabetic nephropathy. Clin J Am Soc Nephrol 2(6):1306–1316. doi:10.2215/CJN.02560607
Brownlee M (2001) Biochemistry and molecular cell biology of diabetes complications. Nature 414:813–820. doi:10.1038/414813a
Nishikawa T, Edelstein D, Du XL et al (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404:787–790. doi:10.1038/35008121
Maritm AC, Sanders RA, Watkins JB (2003) Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 17(1):24–38. doi:10.1002/jbt.10058
Newsholme P, Haber EP, Hirabara SM et al (2007) Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity. J Phys 583(Pt 1):9–24. doi:10.1113/jphysiol.2007.135871
Sutton A, Khoury H, Prip-Buus C et al (2003) The Ala16Val genetic dimorphism modulates the import of human manganese superoxide dismutase into rat liver mitochondria. Pharmacogenetics 13:145–157. doi:10.1097/00008571-200303000-00004
Shimoda-Matsubayashi S, Matsumine H, Kobayashi T et al (1996) Structural dimorphism in the mitochondrial targeting sequence in the human manganese superoxide dismutase gene. Biochem Biophys Res Commun 226:561–565. doi:10.1006/bbrc.1996.1394
Nomiyama T, Tanaka Y, Piao L et al (2003) The polymorphism of manganese superoxide dismutase is associated with diabetic nephropathy in Japanese type 2 diabetic patients. J Hum Genet 48:138–141
Lee SJ, Choi MG, Kim DS, Kim TW et al (2006) Manganese superoxide dismutase gene polymorphism (V16A) is associated with stages of albuminuria in Korean type 2 diabetic patients. Metabolism 55:1–7. doi:10.1016/j.metabol.2005.04.030
Möllsten A, Marklund SL, Wessman M et al (2007) A functional polymorphism in the manganese superoxide dismutase gene and diabetic nephropathy. Diabetes 56(1):265–269. doi:10.2337/db06-0698
Nakanishi S, Yamane K, Ohishi W et al (2008) Manganese superoxide dismutase Ala16Val polymorphism is associated with the development of type 2 diabetes in Japanese-Americans. Diabetes Res Clin Pract 81(3):381–385. doi:10.1016/j.diabres.2008.06.003
The Expert committee on the Diagnosis and Classification of Diabetes Mellitus (Position statement) (2003) Diabetes Care 26 (suppl l): S5–S20
Molitch ME, DeFronzo RA, Franz MJ et al (2004) American Diabetes Association. Nephropathy in diabetes. Diabetes Care 27(suppl l):S79–S83. doi:10.2337/diacare.27.5.1240-a
Sharma R, Sharma M, Datta PK et al (2002) Induction of metallothionein-I protects glomeruli from superoxide-mediated increase in albumin permeability. Exp Biol Med (Maywood) 227(1):26–31
Wolf G, Ziyadeh FN (2007) Cellular and molecular mechanism of proteinuria in diabetic nephropathy. Nephron Physiol 106(2):26–31. doi:10.1159/000101797
McCord JM, Fridovich I (1988) Superoxide dismutase: the first twenty years (1968–1988). Free Radic Biol Med 5(5–6):363–369. doi:10.1016/0891-5849(88)90109-8
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This research was supported by grants from the Project of National Nature Science Foundation of China (39900071) and Project of Shanghai Shenkang Hospital Development Center (SHDC12007101).
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Liu, L., Zheng, T., Wang, N. et al. The manganese superoxide dismutase Val16Ala polymorphism is associated with decreased risk of diabetic nephropathy in Chinese patients with type 2 diabetes. Mol Cell Biochem 322, 87–91 (2009). https://doi.org/10.1007/s11010-008-9943-x
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DOI: https://doi.org/10.1007/s11010-008-9943-x