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Association of SUMO4 Met55Val variation with increased insulin resistance in newly diagnosed type 2 diabetes in a Chinese population

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Summary

SUMO4 Met55Val variation was shown to be related to type 2 diabetes susceptibility and the vascular complications in Asian people. To further examine the related mechanisms, this study was designed to evaluate the association of SUMO4 Met55Val polymorphism with insulin resistance and β cell function in newly diagnosed type 2 diabetic patients in a Chinese population. Four hundred and twenty seven newly diagnosed type 2 diabetic patients were selected for SUMO4 Met55Val polymorphism genotype analysis. All subjects underwent a 75-g oral glucose tolerance test (OGTT) to estimate the insulin sensitivity and β cell function. Anthropometrics and a metabolic profile were used for phenotyping analysis. The results showed that the SUMO4 Met55Val polymorphism was associated with higher insulin resistance (P<0.001) and lower insulin sensitivity (P<0.001). Patients with GG genotype had higher levels of plasma glucose, insulin and C peptide. Insulin sensitivity index (ISI) was closely correlated with body mass index (BMI) in patients with GG genotype in comparison to the counterparts with AG or AA genotype (r= −0.504 vs. r= −0.430 vs. r= −0.340). Multiple regression linear analysis showed that SUMO4 Met55Val polymorphism was an independent determinant for insulin sensitivity (P=0.001), which, along with triglyceride, BMI and sex, could account for 20.1% of the variation in ISI. The result remained the same after adjusting for BMI and sex. No association was found between SUMO4 Met55Val polymorphism and β cell function (all P>0.05). It was concluded that SUMO4 Met55Val variant was associated with increased insulin resistance in Chinese patients with newly diagnosed type 2 diabetes.

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References

  1. Guo D, Li M, Zhang Y, et al. A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes. Nat Genet, 2004, 36(8):837–841

    Article  PubMed  CAS  Google Scholar 

  2. Zou YF, Feng XL, Tao JH, et al. Association of SUMO4 MET55VAL polymorphism with susceptibility to autoimmune and inflammatory diseases: a meta-analysis. Int J Immunogenet, 2010, 37(5):345–354

    Article  PubMed  CAS  Google Scholar 

  3. Noso S, Ikegami H, Fujisawa T, et al. Genetic heterogeneity in association of the SUMO4 M55V variant with susceptibility to type 1 diabetes. Diabetes, 2005, 54(12):3582–3586

    Article  PubMed  CAS  Google Scholar 

  4. Aribi M. Candidate genes implicated in type 1 diabetes susceptibility. Curr Diabetes Rev, 2008, 4(2):110–121

    Article  PubMed  CAS  Google Scholar 

  5. Sang Y, Zong W, Liu M, et al. Association of SUMO4 M55V polymorphism with type 1 diabetes in Chinese children. J Pediatr Endocrinol Metab, 2010, 23(10): 1083–1086

    Article  PubMed  CAS  Google Scholar 

  6. Noso S, Fujisawa T, Kawabata Y, et al. Association of small ubiquitin-like modifier 4 (SUMO4) variant, located in IDDM5 locus, with type 2 diabetes in the Japanese population. J Clin Endocrinol Metab, 2007, 92(6): 2358–2362

    Article  PubMed  CAS  Google Scholar 

  7. Shimada T, Furukawa Y, Furuta H, et al. SUMO4 Met55Val polymorphism is associated with coronary heart disease in Japanese type 2 diabetes individuals. Diabetes Res Clin Pract, 2009, 85(1):85–89

    Article  PubMed  CAS  Google Scholar 

  8. Lin HY, Li SL, Yu ML, et al. Small ubiquitin-like modifier-4 Met55Val polymorphism is associated with glycemic control of Type 2 diabetes mellitus in Taiwan. J Endocrinol Invest, 2010, 33(6):401–405

    PubMed  CAS  Google Scholar 

  9. Lin HY, Wang CL, Hsiao PJ, et al. SUMO4 MET55VAL variant is associated with diabetic nephropathy in type 2 diabetes. Diabetes, 2007, 56(4):1177–1180

    Article  PubMed  CAS  Google Scholar 

  10. Hotamisligil GS. Inflammation and metabolic disorders. Nature, 2006, 444(7121):860–867

    Article  PubMed  CAS  Google Scholar 

  11. Bourlier V, Bouloumie A. Role of macrophage tissue infiltration in obesity and insulin resistance. Diabetes Metab, 2009, 35(4):251–260

    Article  PubMed  CAS  Google Scholar 

  12. Fuentes L, Roszer T, Ricote M. Inflammatory mediators and insulin resistance in obesity: role of nuclear receptor signaling in macrophages. Mediators Inflamm, 2010, 2010:219583

    Article  PubMed  Google Scholar 

  13. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance. Science, 1993, 259(5091): 87–91

    Article  PubMed  CAS  Google Scholar 

  14. Herder C, Schneitler S, Rathmann W, et al. Low-grade inflammation, obesity, and insulin resistance in adolescents. J Clin Endocrinol Metab, 2007, 92(12):4569–4574

    Article  PubMed  CAS  Google Scholar 

  15. Bonora E, Targher G, Alberiche M, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care, 2001, 23(1):57–63

    Article  Google Scholar 

  16. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care, 1999, 22(9):1462–1470

    Article  PubMed  CAS  Google Scholar 

  17. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 1985, 28(7):412–419

    Article  PubMed  CAS  Google Scholar 

  18. Hanson RL, Pratley RE, Bogardus C, et al. Evaluation of simple indices of insulin sensitivity and insulin secretion for use in epidemiologic studies. Am J Epidemiol, 2000, 151(2):190–198

    PubMed  CAS  Google Scholar 

  19. Cai D, Yuan M, Frantz DF, et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB. Nat Med, 2005, 11(2):183–190

    Article  PubMed  CAS  Google Scholar 

  20. Yang J, Park Y, Zhang H, et al. Feed-forward signaling of TNF-alpha and NF-kappaB via IKK-beta pathway contributes to insulin resistance and coronary arteriolar dysfunction in type 2 diabetic mice. Am J Physiol Heart Circ Physiol, 2009, 296(6):H1850–1858

    Article  PubMed  CAS  Google Scholar 

  21. Gao Z, Yin J, Zhang J, et al. Inactivation of NF-kappaB p50 leads to insulin sensitization in liver through post-translational inhibition of p70S6K. J Biol Chem, 2009, 284(27):18368–18376

    Article  PubMed  CAS  Google Scholar 

  22. Wang CY, Yang P, Li M, et al. Characterization of a negative feedback network between SUMO4 expression and NFkappaB transcriptional activity. Biochem Biophys Res Commun, 2009, 381(4):477–481

    Article  PubMed  CAS  Google Scholar 

  23. Wang CY, She JX. SUMO4 and its role in type 1 diabetes pathogenesis. Diabetes Metab Res Rev, 2008, 24(2): 93–102

    Article  PubMed  CAS  Google Scholar 

  24. Pirola L, Johnston AM, Van Obberghen E. Modulation of insulin action. Diabetologia, 2004, 47(2):170–184

    Article  PubMed  CAS  Google Scholar 

  25. Sengupta U, Ukil S, Dimitrova N, et al. Expression-based network biology identifies alteration in key regulatory pathways of type 2 diabetes and associated risk/complications. PLoS One, 2009, 4(12):e8100

    Article  PubMed  Google Scholar 

  26. Wei W, Yang P, Pang J, et al. A stress-dependent SUMO4 sumoylation of its substrate proteins. Biochem Biophys Res Commun, 2008, 375(3):454–4592

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China

    Zhenzhong Ji  (季振中), Zhe Dai  (代 喆), Yan Huang  (黄 艳), Hedson Alves Martins & Yancheng Xu  (徐焱成)

Authors
  1. Zhenzhong Ji  (季振中)
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  2. Zhe Dai  (代 喆)
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  3. Yan Huang  (黄 艳)
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  4. Hedson Alves Martins
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  5. Yancheng Xu  (徐焱成)
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Corresponding author

Correspondence to Yancheng Xu  (徐焱成).

Additional information

This project was supported by a grant from the National Natural Sciences Foundation of China (No. 30871188) and the National Natural Sciences Foundation of Hubei Province (No. 303131486).

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Ji, Z., Dai, Z., Huang, Y. et al. Association of SUMO4 Met55Val variation with increased insulin resistance in newly diagnosed type 2 diabetes in a Chinese population. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 31, 306–311 (2011). https://doi.org/10.1007/s11596-011-0372-9

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  • DOI: https://doi.org/10.1007/s11596-011-0372-9

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