Variable number of tandem repeats (VNTR) polymorphism in the interleukin 4 (IL-4) gene has been associated with end-stage renal disease (ESRD) subjects in many different populations, although with conflicting results. We determined the 70 bp of VNTR polymorphism at intron 3 of the IL-4 gene in Malaysian ESRD subjects. Buccal cells were collected from 160 case and 160 control subjects; genomic DNA was amplified using PCR, followed by agarose gel electrophoresis. There were significant differences in genotypes and alleles of the IL-4 gene. We conclude that VNTR polymorphism of the IL-4 gene is a risk factor for the development of ESRD among Malaysians.
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.