Original Article

Different Risk Indictors of Diabetic Nephropathy in Transforming Growth Factor-beta1 T869C CC/CT Genotype and TT Genotype


Background: Transforming growth factor-beta 1(TGF-β1) T869C (rs1800470, the same below) gene polymorphism is notably relative with the development of Diabetic Nephropathy (DN),and CC/CT genotype diabetic have higher frequency of than TT genotype diabetic. To find out individual risk factors in the two genotypes especially in susceptible genotype could provide more efficient and targeted prevention.

Methods: This was a prospective cohort study.  A total of 251 type 2 diabetes mellitus (T2DM) patients [53.4% male, 56(52-67) years] were enrolled in this cohort study. Multiple concerned factors were collected and the relationship of these risk factors and development of DN were evaluated by Cox regression analysis. Hazard ratios of development of DN were calculated by Kaplan-Meier curves and the Cox proportional hazards model for CC/CT genotype versus TT genotype patients.

Results: TGF-β1 T869C gene polymorphism was an independent predictor of DN in T2DM patients (HR, 2.08; 95%CI, 1.18-3.66; P=0.012). Hyperlipemia (HR, 1.91; 95%CI, 1.19-3.08; P=0.007), age (HR, 0.95; 95%CI, 0.93-0.98; P=0.001) and smoking status (HR, 2.36; 95%CI, 1.07-5.21; P=0.033) were risk indictors of the development of DN in CC/CT genotype patients. HbA1c (HR, 2.8; 95%CI, 1.07-7.30; P=0.036), hypertension (HR, 7.46; 95%CI, 1.38-40.29; P=0.02), and hyperlipemia (HR, 12.33; 95%CI, 1.05-145.39; P=0.046) were risk indictors for the development of DN in TT genotype patients.

Conclusion: TGF-β1 T869C gene polymorphism was an independent predictor of DN for T2DM patients and CC/CT genotype had higher susceptibility to DN. CC/CT genotype and TT genotype patients had different risk indictors of DN.


Collins AJ, Kasiske B, Herzog C, et al. (2007). Ex¬cerpts from the United States Renal Da-ta Sys¬tem 2006 Annual Data Report. Am J Kidney Dis, 49(1 Suppl 1):A6-7.

Yang XL, So WY, Kong AP, et al. (2006). End-stage renal disease risk equations for Hong Kong Chinese patients with type 2 diabetes: Hong Kong Diabetes Registry. Diabetologia, 49(10): 2299-2308.

Telishevka M, Chenett L, McKee M (2001). To¬wards an understanding of the high death rate among young people with dia-betes in Ukraine. Diabet Med, 18(1): 3-9.

Pettitt DJ, Saad MF, Bennett PH, Nelson RG, Knowler WC (1990). Familial predisposi-tion to renal disease in two generations of Pima In¬dians with type 2 (non-insulin-dependent) dia¬betes mellitus. Diabetologia, 33(7): 438-443.

Wong TY, Poon P, Chow KM, Szeto CC, Cheung MK, Li PK (2003). Association of transforming growth factor-beta (TGF-beta) T869C (Leu 10Pro) gene polymor-phisms with type 2 dia¬betic nephropathy in Chinese. Kidney Int, 63(5): 1831-1835.

Xu K, Liu X, Yang F, et al. (2013). PAI-1 -675 4G/5G polymorphism in association with di¬a¬betes and diabetic complications sus-ceptibil¬ity: a meta-analysis study. PloS One, 8(11): e79150.

Dennler S, Gouman MJ, ten Dijke P (2002). Trans¬forming growth factor signal trans-duc¬tion. J Leukoc Biol, 71: 731-740.

Barnette DN, Hulin A, Ahmed AS, Colige AC, Azhar M, Lincoln J (2013). Tgfbeta-Smad and MAPK signaling mediate scleraxis and proteo¬glycan expression in heart valves. J Mol Cell Car¬diol, 65: 137-146.

WA BTY, NA N (1996). Transforming growth factor beta in diabetic nephropathy. Diabetes Metab Rev, 12(4): 309-339.

Buraczynska M, Baranowicz-Gaszczyk I, Bor-o¬wicz E, Ksiazek A (2007). TGF-beta1 and TSC-22 gene polymorphisms and suscep-tibil¬ity to microvascular complications in type 2 di¬abetes. Nephron Physiol, 106(4):p69-75.

Jia H, Yu L, Gao B, Ji Q (2011). Association be¬tween the T869C polymorphism of trans¬form¬ing growth factor-beta 1 and di-abetic nephrop¬athy: a meta-analysis. Endo-crine, 40(3): 372-378.

Mou X, Liu WH, Zhou DY, et al. (2011). As-soci¬a¬tion of Chinese medicine constitution suscep¬ti¬bility to diabetic nephropathy and transform¬ing growth factor-beta1 (T869C) gene poly¬mor¬phism. Chin J Integr Med, 17(9): 680-684.

The Chinese Diabetes Society of the Chinese Med¬ical Association. China Guideline for Dia-betes. Bei¬jing: Peking University Medical Press; 2003: 10.

Mogensen CE. Early Diabetic Renal Involvelent and Nephropathy: Elsevier Science publishers; 1987: 306.

Kopp JB, Factor VM, Mozes M, et al. (1996). Transgenic mice with increased plasma levels of TGF-beta 1 develop progressive renal dis¬ease. Lab Invest, 74(6): 991-1003.

Mason RM, Wahab NA (2003). Extracellular ma¬trix metabolism in diabetic nephropathy. J Am Soc Nephrol, 14(5): 1358-1373.

Sharma K, Ziyadeh FN (1994). Renal hyper-tro¬phy is associated with upregulation of TGF-beta 1 gene expression in diabetic BB rat and NOD mouse. Am J Physiol, 267(6 Pt 2): F1094-1001.

Li W, Wu H, Song C (2013). TGF-β1 -509C/T (or +869T/C) polymorphism might be not associated with hepatocellular carcinoma risk. Tumour Biol, 34(5): 2675-81.

Guerra JL, Gomez D, Wei Q, et al. (2012). Asso¬ci¬ation between single nucleotide pol-ymor¬phisms of the transforming growth factor beta1 gene and the risk of severe radiation esophagitis in patients with lung cancer. Radi¬other Oncol, 105(3): 299-304.

Wang Y, Yang H, Li L, Xia X (2013). An up-dated meta-analysis on the association of TGF-beta1 gene promoter -509C/T pol-ymorphism with colorectal cancer risk. Cy-tokine, 61(1): 181-187.

Chiu CJ, Chang ML, Chiang CP, Hahn LJ, Hsieh LL, Chen CJ (2002). Interaction of collagen-re¬lated genes and susceptibility to betel quid-in¬duced oral submucous fibrosis. Cancer Epi¬demiol Biomarkers Prev, 11(7): 646-653.

Son JY, Kim SY, Cho SH, et al. (2013). TGF-beta1 T869C polymorphism may affect sus¬ceptibility to idiopathic pulmonary fi-brosis and disease se¬verity. Lung, 191(2): 199-205.

El-Sherbini SM, Shahen SM, Mosaad YM, Abdel¬gawad MS, Talaat RM (2013). Gene polymor¬phism of transforming growth factor-beta1 in Egyptian patients with type 2 diabetes and dia¬betic nephropathy. Acta Biochim Biophys Sin (Shanghai), 45(4): 330-338.

Celedon JC, Lange C, Raby BA, et al. (2004). The transforming growth factor-beta1 (TGFB1) gene is associated with chronic obstructive pul¬monary disease (COPD). Hum Mol Genet, 13(15): 1649-1656.

Suthanthiran M, Li B, Song JO, et al. (2000). Trans¬forming growth factor-beta 1 hyper-ex¬pression in African-American hyperten-sives: A novel mediator of hypertension and/or target organ damage. Proc Natl Acad Sci U S A, 97(7): 3479-3484.

Yamada Y, Miyauchi A, Takagi Y, Tanaka M, Mi¬zuno M, Harada A (2001). Association of the C-509-->T polymorphism, alone of in combi¬nation with the T869-->C poly-morphism, of the transforming growth factor-beta1 gene with bone mineral densi-ty and genetic suscep¬tibility to osteoporo-sis in Japanese women. J Mol Med (Berl), 79(2-3): 149-156.

Hovind P, Rossing P, Tarnow L, Parving HH (2003). Smoking and progression of dia-betic nephropathy in type 1 diabetes. Diabe-tes Care, 26(3): 911-916.

UK Prospective Diabetes Study Group (1998). Tight blood pressure control and risk of macro¬vascular and microvascular compli-ca¬tions in type 2 diabetes: UKPDS 38. BMJ, 317(7160): 703-13.

Misra A, Kumar S, Kishore Vikram N, Ku-mar A (2003). The role of lipids in the de-velopment of diabetic microvascular com-plications: impli¬ca¬tions for therapy. Am J Cardiovasc Drugs, 3(5): 325-338.

Leiter LA (2005). The prevention of diabetic mi¬crovascular complications of diabetes: is there a role for lipid lowering? Diabetes Res Clin Pract, 68 Suppl 2: S3-14.

Toth PP, Simko RJ, Palli SR, Koselleck D, Quimbo RA, Cziraky MJ (2012). The im-pact of serum lipids on risk for microan-giopathy in pa¬tients with type 2 diabetes mellitus. Cardiovasc Diabetol, 11: 109.

Hoffman BB, Sharma K, Zhu Y, Ziyadeh FN (1998). Transcriptional activation of trans-form¬ing growth factor-beta1 in mesangial cell culture by high glucose concentration. Kidney Int, 54(4): 1107-1116.

Barzilay J, Warram JH, Bak M, Laffel LM, Canessa M, Krolewski AS (1992). Predis-posi¬tion to hy¬pertension: risk factor for nephropa¬thy and hy¬pertension in IDDM. Kidney Int, 41(4): 723-730.

Chuahirun T, Wesson DE (2002). Cigarette smok¬ing predicts faster progression of type 2 estab¬lished diabetic nephropathy despite ACE inhi¬bition. Am J Kidney Dis, 39(2): 376-382.

O'Meara ES, White M, Siscovick DS, Lyles MF, Kuller LH (2005). Hospitalization for pneu¬mo¬nia in the Cardiovascular Health Study: in¬ci¬dence, mortality, and influence on longer-term survival. J Am Geriatr Soc, 53(7): 1108-1116.

Yende S, Angus DC, Ali IS, et al. (2007). In-fluence of comorbid conditions on long-term mortal¬ity after pneumonia in older people. J Am Ger¬iatr Soc, 55(4): 518-525.

IssueVol 45 No 6 (2016) QRcode
SectionOriginal Article(s)
TGF-β1 Diabetic nephropathy T869C Risk Type 2 diabetes mellitus

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MOU X, LIU Y, ZHOU D, HU Y, MA G, SHOU C, CHEN J, ZHOU D. Different Risk Indictors of Diabetic Nephropathy in Transforming Growth Factor-beta1 T869C CC/CT Genotype and TT Genotype. Iran J Public Health. 2016;45(6):761-767.