Identification of reference housekeeping-genes for mRNA expression studies in patients with type 1 diabetes

Mol Cell Biochem. 2016 Jun;417(1-2):49-56. doi: 10.1007/s11010-016-2712-3. Epub 2016 May 9.

Abstract

Selection of appropriate housekeeping-genes as reference is important in mRNA expression-related experiments. It is more important in diabetes since hyperglycemia per se can influence expression of housekeeping-genes. RNA expression of Glyceraldehyde-3-phosphate-dehydrogenase, β-actin and 18S-ribosomal-RNA, Hypoxanthine-phosphoribosyl-transferase (HPRT), Tyrosine-3-monooxygenase/tryptophan (YHWAZ), β2-microglobin (β2M), TATA-binding-protein (TBP), and Ubiquitin C and cytochrome1 (CYC1) assessed in circulating-lymphocytes-(PBMC) of patients with type-1-diabetes and healthy controls. The stability ('M' value <1.02) and number of housekeeping-genes required for normalization in qRT-PCR were determined by 'ge-norm software.' Vitamin-D-receptor (VDR) was used as a target gene. All the nine genes tested had sufficient 'M' value in diabetes and healthy controls. However, housekeeping-genes indicated a relatively higher stability of expression in healthy controls in comparison to diabetes. Use of single housekeeping-genes brought gross variation in the calculation of VDR-mRNA copies. The ge-norm software suggested geometric mean of five housekeeping-genes for ideal normalization in diabetes (CYC1, β-actin, YHWAZ, HPRT, and β2M) and only three in controls (CYC1, β-actin, and TBP). HbA1c did not correlate with expression of any of the nine housekeeping-genes. Thus, geometric mean of CYC1, β-actin, YHWAZ, HPRT, and β2M needs to be used for ideal normalization of mRNA in type-1-diabetes. Similar studies are required in other population.

Keywords: Gene expression; Housekeeping-genes; Type 1 diabetes; Vitamin D receptor.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Diabetes Mellitus, Type 1* / genetics
  • Diabetes Mellitus, Type 1* / metabolism
  • Female
  • Gene Expression Profiling* / methods
  • Gene Expression Profiling* / standards
  • Gene Expression Regulation*
  • Genes, Essential*
  • Humans
  • Male
  • RNA, Messenger* / biosynthesis
  • RNA, Messenger* / genetics
  • Reverse Transcriptase Polymerase Chain Reaction* / methods
  • Reverse Transcriptase Polymerase Chain Reaction* / standards

Substances

  • RNA, Messenger