Association of BsmI Polymorphisms in Vitamin D Receptor Gene With Diabetic Kidney Disease

Overview

Background: Diabetic kidney disease (DKD), as one of chronic complication of type 2 diabetes mellitus, is common cause of end stage renal disease (ESRD). Vitamin D deficiency is known as one of DKD risk factors. Recent studies on association between vitamin D deficiency and DKD had shown conflicting results. It may be due to vitamin D receptor gene polymorphisms, which is affected by BsmI, Cdx2, ApaI, FokI, and TaqI gene. The investigators conducted cross-sectional study to investigate association between BsmI polymorphisms in vitamin D receptor gene with diabetic kidney disease

Hypothesis: BsmI polymorphisms in vitamin D receptor gene is associated with diabetic kidney disease (DKD)

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Cross-Sectional
  • Study Primary Completion Date: March 2015

Detailed Description

Diabetic kidney disease (DKD) is a common cause of end stage renal disease (ESRD). Data from Indonesian Renal Registry (2011) revealed that 25% etiology of patients who underwent hemodialysis is DKD. Risk factors that are associated with DKD include blood glucose control, hypertension, dyslipidemia, duration of diabetes mellitus, high body mass index (BMI), age, sex, ethnicity, vitamin D deficiency, high sodium diet, high protein diet, and smoking.

The roles of vitamin D that are related to kidney are inhibition of renin transcription process, angiotensin II, renal inflammation process, and albumin excretion, prevention of podocytes damage, glomerulosclerosis process, and transformation from kidney epithelial cell into mesenchymal cell. Current studies on association between vitamin D deficiency and DKD had shown conflicting results. It may be related to genetic factor which is vitamin D receptor polymorphisms. The vitamin D receptor polymorphism is affected by Cdx2, ApaI, BsmI, FokI, and TaqI gene, where Asian population is mostly affected by ApaI, FokI, and Cdx2.

Several studies had reported the association between BsmI polymorphisms in vitamin D receptor gene and DKD in various population. Zhang, et al (2012) study revealed the association between BsmI polymorphisms in vitamin D receptor gene and DKD in Han Chinese population, while study from Vedralova, et al (2012) in Caucasian race showed opposite result. However, the association between BsmI polymorphism in vitamin D receptor gene and DKD has not been investigated in Indonesian-Malay race.

This is a cross-sectional study that investigate the association between BsmI polymorphisms in vitamin D receptor gene and DKD in Indonesian-Malay race. The investigators collected data about study participants' characteristics, conducted physical examination and laboratory examination, which include BsmI polymorphisms in vitamin D receptor gene.

Arms, Groups and Cohorts

  • Bb Genotype
    • Subjects with Bb genotype of BsmI polymorphisms in vitamin D receptor gene
  • bb Genotype
    • Subjects with bb genotype of BsmI polymorphisms in vitamin D receptor gene

Clinical Trial Outcome Measures

Primary Measures

  • Association between BsmI Polymorphisms in Vitamin D Receptor Gene and Diabetic Kidney Disease
    • Time Frame: 1 month
    • This study investigated association between BsmI polymorphisms in vitamin D receptor gene with diabetic kidney disease

Participating in This Clinical Trial

Inclusion Criteria

  • Type 2 diabetes mellitus patient
  • Indonesian-Malay race
  • Had signed the informed consent

Exclusion Criteria

  • Urinary tract infection
  • Pregnant patient
  • Fever
  • In menstrual period
  • Had undergone hemodialysis or peritoneal dialysis
  • Had used non steroid antiinflammatory drugs (NSAIDs)
  • Postexercise

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Indonesia University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Pringgodigdo Nugroho, MD, Head of Dialysis Unit, Dr Cipto Mangunkusumo General Hospital – Indonesia University
  • Overall Official(s)
    • Pringgodigdo Nugroho, MD, Principal Investigator, Indonesia University
    • Suhardjono, Prof., MD, PhD, Principal Investigator, Indonesia University
    • Aida Lydia, MD, PhD, Principal Investigator, Indonesia University
    • Kuntjoro Harimurti, MD, PhD, Principal Investigator, Indonesia University
    • Dekta Filantropi Esa, MD, Principal Investigator, Indonesia University

Citations Reporting on Results

Perhimpunan Nefrologi Indonesia. Report of Indonesian Renal Registry. Jakarta; 2011.

Ramachandran A, Snehalatha C, Shetty AS, Nanditha A. Trends in prevalence of diabetes in Asian countries. World J Diabetes. 2012 Jun 15;3(6):110-7. doi: 10.4239/wjd.v3.i6.110.

Zhao HL, Thomas GN, Leung W, Tomlinson B, Hsu YH, Chan P. An update on the management of nephropathy in type 2 diabetes. J Chin Med Assoc. 2003 Nov;66(11):627-36. Review.

Tseng CH. Lipid abnormalities associated with urinary albumin excretion rate in Taiwanese type 2 diabetic patients. Kidney Int. 2005 Apr;67(4):1547-53.

Vedovato M, Lepore G, Coracina A, Dodesini AR, Jori E, Tiengo A, Del Prato S, Trevisan R. Effect of sodium intake on blood pressure and albuminuria in Type 2 diabetic patients: the role of insulin resistance. Diabetologia. 2004 Feb;47(2):300-3. Epub 2003 Dec 24.

Dullaart RP, Beusekamp BJ, Meijer S, van Doormaal JJ, Sluiter WJ. Long-term effects of protein-restricted diet on albuminuria and renal function in IDDM patients without clinical nephropathy and hypertension. Diabetes Care. 1993 Feb;16(2):483-92.

Abbasi MA, Abro A, Sheikh M. Smoking is related to albumin excretion in type 2 diabetes mellitus. Pak J Physiol. 2006;2(2):45-8.

Koroshi A, Idrizi A. Renoprotective effects of Vitamin D and renin-angiotensin system. Hippokratia. 2011 Oct;15(4):308-11. Review.

Bid HK, Konwar R, Aggarwal CG, Gautam S, Saxena M, Nayak VL, Banerjee M. Vitamin D receptor (FokI, BsmI and TaqI) gene polymorphisms and type 2 diabetes mellitus: a North Indian study. Indian J Med Sci. 2009 May;63(5):187-94. doi: 10.4103/0019-5359.53164.

Zhang H, Wang J, Yi B, Zhao Y, Liu Y, Zhang K, Cai X, Sun J, Huang L, Liao Q. BsmI polymorphisms in vitamin D receptor gene are associated with diabetic nephropathy in type 2 diabetes in the Han Chinese population. Gene. 2012 Mar 10;495(2):183-8. doi: 10.1016/j.gene.2011.12.049. Epub 2012 Jan 5.

Vedralová M, Kotrbova-Kozak A, Zelezníková V, Zoubková H, Rychlík I, Cerná M. Polymorphisms in the vitamin D receptor gene and parathyroid hormone gene in the development and progression of diabetes mellitus and its chronic complications, diabetic nephropathy and non-diabetic renal disease. Kidney Blood Press Res. 2012;36(1):1-9. doi: 10.1159/000339021. Epub 2012 Jun 18.

Dewi K. Penurunan fungsi ginjal pada pasien DM tipe 2 di Poliklinik Endokrin Metabolik RSUPN Cipto Mangunkusumo. University of Indonesia; 2007.

Indra T. Asosiasi antara status vitamin D (25(OH)D) dengan albuminuria pada pasien diabetes melitus tipe 2. University of Indonesia; 2013.

Giunti S, Barit D, Cooper ME. Mechanisms of diabetic nephropathy: role of hypertension. Hypertension. 2006 Oct;48(4):519-26. Epub 2006 Sep 4. Review.

Bayliss G, Weinrauch LA, D'Elia JA. Pathophysiology of obesity-related renal dysfunction contributes to diabetic nephropathy. Curr Diab Rep. 2012 Aug;12(4):440-6. doi: 10.1007/s11892-012-0288-1. Review.

Abbate M, Zoja C, Remuzzi G. How does proteinuria cause progressive renal damage? J Am Soc Nephrol. 2006 Nov;17(11):2974-84. Epub 2006 Oct 11. Review.

Nosratabadi R, Arababadi MK, Salehabad VA, Shamsizadeh A, Mahmoodi M, Sayadi AR, Kennedy D. Polymorphisms within exon 9 but not intron 8 of the vitamin D receptor are associated with the nephropathic complication of type-2 diabetes. Int J Immunogenet. 2010 Dec;37(6):493-7. doi: 10.1111/j.1744-313X.2010.00953.x. Epub 2010 Aug 19.

Inassi J, Vijayalakshmy R. Role of duration of diabetes in the development of nephropathy in type 2 diabetic patients. Natl J Med Res. 2013;3(1):8-11.

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