Effect of a Novel Mutation in 5′-Regulatory Region of Aldose Reductase Gene on Its Expression

Ping Xie, Qingjie Li, Mei Lian Liu, Jian Jun Huang, Wei Min Zeng, Shu Hua Chen, Hui Ping Song

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

To study the genetic variation in 5′-regulatory region of aldose reductase (AR) gene that might influence expression and the relationship between variations and diabetic complication (DC), PCR-single stranded conformational polymorphism (SSCP) was used to screen the 5′-regulatory region of AR gene in Chinese patients with type 2 diabetes mellitus. A novel mutation, C-167-→A substitution which created a new CCAAT box was found only in two diabetic patients. These two patients have no retinopathy, and the AR activity of their erythrocytes was within low range in patients without DC. The DNA segments of AR wild type and mutant were subcloned into pCAT reporter vector, and CAT assays were performed to assess promoter activity. The interaction between the DNA segments and nuclear proteins was determined by using competitive gel electrophoretic mobility shift assay (EMSA). The transcriptional activity of mutant (5.7% ± 2.9%) was lower than that of wild type (15.7% ± 4.1%) (P < 0.01), and the mobility shift of mutant was also slower than that of wild type. The results indicated the mutation C-167-→A in AR gene might prevent or delay the development of DC by repressing the expression of AR gene.

Original languageEnglish (US)
Pages (from-to)904-908
Number of pages5
JournalActa Biochimica et Biophysica Sinica
Volume35
Issue number10
StatePublished - 2003
Externally publishedYes

Fingerprint

Aldehyde Reductase
Nucleic Acid Regulatory Sequences
Genes
Mutation
Diabetes Complications
Assays
Single-Stranded Conformational Polymorphism
Electrophoretic mobility
DNA
Electrophoretic Mobility Shift Assay
Medical problems
Nuclear Proteins
Polymorphism
Type 2 Diabetes Mellitus
Substitution reactions
Erythrocytes
Gels
Polymerase Chain Reaction

Keywords

  • Aldose reductase
  • Diabetic complication
  • Gene
  • Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

Cite this

Xie, P., Li, Q., Liu, M. L., Huang, J. J., Zeng, W. M., Chen, S. H., & Song, H. P. (2003). Effect of a Novel Mutation in 5′-Regulatory Region of Aldose Reductase Gene on Its Expression. Acta Biochimica et Biophysica Sinica, 35(10), 904-908.

Effect of a Novel Mutation in 5′-Regulatory Region of Aldose Reductase Gene on Its Expression. / Xie, Ping; Li, Qingjie; Liu, Mei Lian; Huang, Jian Jun; Zeng, Wei Min; Chen, Shu Hua; Song, Hui Ping.

In: Acta Biochimica et Biophysica Sinica, Vol. 35, No. 10, 2003, p. 904-908.

Research output: Contribution to journalArticle

Xie, P, Li, Q, Liu, ML, Huang, JJ, Zeng, WM, Chen, SH & Song, HP 2003, 'Effect of a Novel Mutation in 5′-Regulatory Region of Aldose Reductase Gene on Its Expression', Acta Biochimica et Biophysica Sinica, vol. 35, no. 10, pp. 904-908.
Xie, Ping ; Li, Qingjie ; Liu, Mei Lian ; Huang, Jian Jun ; Zeng, Wei Min ; Chen, Shu Hua ; Song, Hui Ping. / Effect of a Novel Mutation in 5′-Regulatory Region of Aldose Reductase Gene on Its Expression. In: Acta Biochimica et Biophysica Sinica. 2003 ; Vol. 35, No. 10. pp. 904-908.
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