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KMID : 0354720070310030274
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Journal of Korean Diabetes Association
2007 Volume.31 No. 3 p.274 ~ p.283
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The Association of Aldose Reductase Gene Polymorphisms with Neuropathy in Patients with Type 2 Diabetes
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Jeong In-Kyong
Park Kyong-Soo
Moon Min-Kyong
Kim Jae-Hyun
Shin Chan-Soo
Kim Seong-Yeon
Lee Hong-Kyu
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Abstract
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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.
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KEYWORD
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Diabetic neuropathy, Microsatellite, polymorphism, (A-C)n dinucleotide
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