J Korean Diabetes Assoc.  2007 May;31(3):274-283. 10.4093/jkda.2007.31.3.274.

The Association of Aldose Reductase Gene Polymorphisms with Neuropathy in Patients with Type 2 Diabetes

• Jeong IK
• Park KS
• Moon MK
• Kim JH
• Shin CS
• Kim SY
• Lee HK

• KMID: 1523016
• DOI: http://doi.org/10.4093/jkda.2007.31.3.274

Abstract

BACKGROUND: Previous studies have suggested that polymorphisms in and around the aldose reductase (AR) gene are associated with the development of diabetic microvascular disease. This study explored the hypothesis that the polymorphisms of the (A-C)n dinucleotide repeat sequence, located at 2.1 kilobase (kb) upstream of the transcription start site of AR gene, modulate the risk of diabetic neuropathy (DN).
METHODS
66 patients with DN, 30 without microvascular complications (MC) after 20 years of diabetes, and 87 normal healthy controls were studied. To test highly polymorphic microsatellite marker 2.1 kb upstream of the initiation site of the AR gene, we performed polymerase chain reaction using the primer labeled with fluorescent dye and GeneScan by ABI prism 377 automated DNA sequencer and ABI Genotyper software 2.0.
RESULTS
Seven alleles (Z-6, Z-4, Z-2, Z, Z+2, Z+4 and Z+6) were identified. Z-2 allele was more frequently observed in patients with DN (77.3%) than in those without MC (43.3%, P = 0.007). The subgroup of patients who developed DN within 5 years after the diagnosis of diabetes also had higher frequency of Z-2 allele (91.7%) compared to those without MC (43.3%, P = 0.028). On the contrary, Z+6 allele tended to be more frequent in patients without MC (10.0%) than in those with DN (0%, P = 0.063).
CONCLUSION
These results support the hypothesis that environmental-genetic interactions may modulate the risk of neuropathy in patients with diabetes. Particularly, the Z-2 allele, in the presence of diabetes, may be associated with the development of DN.

Keyword

Diabetic neuropathy; Microsatellite; polymorphism; (A-C)n dinucleotide

MeSH Terms

Aldehyde Reductase*
Alleles
Diabetic Neuropathies
Diagnosis
Dinucleotide Repeats
DNA
Humans
Microsatellite Repeats
Polymerase Chain Reaction
Transcription Initiation Site
Aldehyde Reductase
DNA

Figure

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  Fig. 1 The results of PCR and electrophoresis with 2% agarose gel.

• 

  Fig. 2 The results of GeneScan by ABI prism 377 automated DNA sequencer and ABI Genotyper software 2.0. The blue-colored peak was the sample labeled FAM and red peakwas internal lane size standard labeled with ROX-500. This example was the homozygote of Z, 23 repeats of (A-C).

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