Skip to main content
Log in

SUMO4 163 G>A variation is associated with kidney disease in Indian subjects with type 2 diabetes

  • Short Communication
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Genetic susceptibility probably plays a role in the development and/or progression of diabetic kidney disease. Small ubiquitin-related modifier 4 (SUMO4) mRNA is expressed in human kidney. Substitution of methionine with valine at codon 55 (M55V) of SUMO4 gene induces higher nuclear factor-kB activity, which is known to mediate the development of kidney disease in individuals with diabetes. We investigated the association between the SUMO4 M55V (rs237025, c.163 G>A) and kidney disease in north Indian subjects with diabetes. A case–control analysis was performed using genomic DNA samples from 216 diabetic patients without nephropathy (DM) and 201 diabetic with nephropathy (DN). The SUMO4 c.163 G>A polymorphism was genotyped using polymerase chain reaction amplification followed by restriction digestion. The duration of diabetes was significantly greater in DN. The genotypic and allelic frequencies were different in DM and DN groups: GG genotype was significantly more frequent in DN as compared to DM (p = 0.018, OR 1.72, 95 % CI 1.1–2.7). Similarly the G allele was more frequent in DN compared to DM (p = 0.017, OR 1.4, 95 % CI 1.1–1.8). This study suggests that SUMO4 c.163 G>A polymorphism is associated with the susceptibility to diabetic nephropathy in north Indian subjects with type 2 diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Koppel H, Riedl E, Braunagel M et al (2011) L-carnosine inhibits high-glucose-mediated matrix accumulation in human mesangial cells by interfering with TGF-beta production and signalling. Nephrol Dial Transplant 26(12):3852–3858

    Article  PubMed  Google Scholar 

  2. Kumar NHP, Sagar S, Vidya J (2011) Diabetic nephropathy—pathogenesis and newer targets in treatment. Int J Pharm Sci Rev Res 6(2):91–105

    Google Scholar 

  3. Quinn M, Angelico MC, Warram JH et al (1996) Familial factors determine the development of diabetic nephropathy in patients with IDDM. Diabetologia 39(8):940–945

    Article  CAS  PubMed  Google Scholar 

  4. Freedman BI, Bostrom M, Daeihagh P et al (2007) Genetic factors in diabetic nephropathy. Clin J Am Soc Nephrol 2(6):1306–1316

    Article  CAS  PubMed  Google Scholar 

  5. Viswanathan V, Zhu Y, Bala K et al (2001) Association between ACE gene polymorphism and diabetic nephropathy in South Indian patients. JOP 2(2):83–87

    CAS  PubMed  Google Scholar 

  6. Mokubo A, Tanaka Y, Nakajima K et al (2006) Chemotactic cytokine receptor 5 (CCR5) gene promoter polymorphism (59029A/G) is associated with diabetic nephropathy in Japanese patients with type 2 diabetes: a 10-year longitudinal study. Diabetes Res Clin Pract 73(1):89–94

    Article  CAS  PubMed  Google Scholar 

  7. Cheema BS, Kohli HS, Sharma R et al (2013) Endothelial nitric oxide synthase gene polymorphisms and renal responsiveness to RAS inhibition therapy in type 2 diabetic Asian Indians. Diabetes Res Clin Pract 99(3):335–342

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. Bohren KM, Nadkarni V, Song JH et al (2004) A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus. J Biol Chem 279(26):27233–27238

    Article  CAS  PubMed  Google Scholar 

  10. Lin HY, Wang CL, Hsiao PJ et al (2007) SUMO4 M55V variant is associated with diabetic nephropathy in type 2 diabetes. Diabetes 56(4):1177–1180

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  12. Rudofsky G Jr, Schlotterer A, Humpert PM et al (2008) A M55V polymorphism in the SUMO4 gene is associated with a reduced prevalence of diabetic retinopathy in patients with Type 1 diabetes. Exp Clin Endocrinol Diabetes 116(1):14–17

    Article  CAS  PubMed  Google Scholar 

  13. Murea M, Ma L, Freedman BI (2012) Genetic and environmental factors associated with type 2 diabetes and diabetic vascular complications. Rev Diabet Stud 9(1):6–22

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sanz AB, Sanchez-Nino MD, Ramos AM et al (2010) NF-kappaB in renal inflammation. J Am Soc Nephrol 21(8):1254–1262

    Article  CAS  PubMed  Google Scholar 

  15. Hofmann MA, Schiekofer S, Kanitz M et al (1998) Insufficient glycemic control increases nuclear factor-kappa B binding activity in peripheral blood mononuclear cells isolated from patients with type 1 diabetes. Diabetes Care 21(8):1310–1316

    Article  CAS  PubMed  Google Scholar 

  16. Mezzano S, Aros C, Droguett A et al (2004) NF-kappaB activation and overexpression of regulated genes in human diabetic nephropathy. Nephrol Dial Transplant 19(10):2505–2512

    Article  CAS  PubMed  Google Scholar 

  17. Nam JS, Cho MH, Lee GT et al (2008) The activation of NF-kappaB and AP-1 in peripheral blood mononuclear cells isolated from patients with diabetic nephropathy. Diabetes Res Clin Pract 81(1):25–32

    Article  CAS  PubMed  Google Scholar 

  18. Guijarro C, Egido J (2001) Transcription factor-kappa B (NF-kappa B) and renal disease. Kidney Int 59(2):415–424

    Article  CAS  PubMed  Google Scholar 

  19. Fallah S, Jafarzadeh M, Hedayati M (2010) No association of the SUMO4 polymorphism M55V variant in type 2 diabetes in Iranian subjects. Diabetes Res Clin Pract 90(2):191–195

    Article  CAS  PubMed  Google Scholar 

  20. Noso S, Fujisawa T, Kawabata Y et al (2007) 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 92(6):2358–2362

    Article  CAS  PubMed  Google Scholar 

  21. Shahsavar F, Jafarzadeh M, Azargoon A et al (2013) Small ubiquitin-like modifier 4 M55V polymorphism is not associated with diabetic nephropathy in Iranian type 2 diabetes patients. Indian J Hum Genet 19(2):179–182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Tang ST, Peng WJ, Wang CJ et al (2012) Polymorphism M55V in gene encoding small ubiquitin-like modifier 4 (SUMO4) protein associates with susceptibility to type 1 (and type 2) diabetes. Diabetes Metab Res Rev 28(8):679–687

    Article  CAS  PubMed  Google Scholar 

  23. Sedimbi SK, Kanungo A, Shastry A et al (2007) No association of SUMO4 M55V with autoimmune diabetes in Asian-Indian patients. Int J Immunogenet 34(2):137–142

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was funded by a grant from Department of Science and Technology, New Delhi, Government of India.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ashok Kumar Yadav.

Ethics declarations

Disclosure

Authors of this manuscript have nothing to disclose.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sinha, N., Yadav, A.K., Kumar, V. et al. SUMO4 163 G>A variation is associated with kidney disease in Indian subjects with type 2 diabetes. Mol Biol Rep 43, 345–348 (2016). https://doi.org/10.1007/s11033-016-3979-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-016-3979-x

Keywords

Navigation