Gene expression profiling in ethnic Malays with type 2 diabetes mellitus, with and without diabetic nephropathy

J Nephrol. Nov-Dec 2011;24(6):778-89. doi: 10.5301/JN.2011.6382.

Abstract

Background: Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD) among type 2 diabetes mellitus patients (DM) in Malaysia. This study used microarray analysis to determine the gene expression profiling in ethnic Malay patients with type 2 DM.

Methods: A total of 312 patients were recruited; 25 were on dialysis due to ESRD, 128 were classified as normoalbuminuric, 93 as microalbuminuric and 66 as macroalbuminuric, based on urine albumin to creatinine ratio of <3.5, between 3.5 and 35 and =35 mg/mmol, respectively.

Results: Microalbuminuria was associated with up- and down-regulation of 2,694 and 2,538 genes, respectively, while macroalbuminuria was associated with up-regulation of 2,520 genes and down-regulation of 2,920 genes. There was significant up-regulation of 1,135 genes and down-regulation of 908 genes in the ESRD samples. Thirty-seven significantly up-regulated genes and 40 down-regulated genes were commonly expressed in all 3 groups of patients with worsening of renal functions. Up-regulated genes included major histocompatibility complex (HLA-C), complement component 3a receptor 1 (C3AR1), solute carrier family 16, member 3 (SLC16A3) and solute carrier family 9 (sodium/hydrogen exchanger) (SLC9A8). Consistently down-regulated genes included were bone morphogenetic phosphatase kinase (BMP2K), solute carrier family 12, member 1 (SLC12A1), solute carrier family 7 (SLC7A2), paternally expressed 10 (PEG10) and protein phosphatase 1 regulatory (inhibitor unit) (PPP1R1C).

Conclusion: This study has identified several genes of interest, such as HLA-C, SLC16A3, SLC9A8, SLC12A1 and SLC7A2, that require verification of their roles as susceptibility genes for diabetic nephropathy in ethnic Malays with type 2 DM.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albuminuria / epidemiology
  • Albuminuria / ethnology
  • Albuminuria / genetics
  • Comorbidity
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / ethnology*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetic Nephropathies / epidemiology
  • Diabetic Nephropathies / ethnology*
  • Diabetic Nephropathies / genetics*
  • Down-Regulation
  • Female
  • Gene Expression Profiling*
  • Humans
  • Kidney Failure, Chronic / epidemiology
  • Kidney Failure, Chronic / ethnology
  • Kidney Failure, Chronic / genetics
  • Malaysia
  • Male
  • Microarray Analysis
  • Middle Aged
  • Renal Dialysis
  • Up-Regulation