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Han, Choi, Park, Lee, and Park: Genetic Association of Mitochondrial DNA Polymorphisms with Type 2 Diabetes Mellitus
Original Article
Korean Diabetes Journal

Korean Diabetes Journal 2009; 33(5): 382-391.

Published online: 31 October 2009

DOI: https://doi.org/10.4093/kdj.2009.33.5.382

Genetic Association of Mitochondrial DNA Polymorphisms with Type 2 Diabetes Mellitus

Tae Su Han1, Jee-Hye Choi1, 2, Jina Park1, 2, Kwang-Ho Lee2, Ae Ja Park1

1Department of Laboratory Medicine, Chung-Ang University College of Medicine, Seoul, Korea.

2Department of Life Science, Chung-Ang University College of Natural Science, Seoul, Korea.

Corresponding author (ajcp@unitel.co.kr)

Received 1 July 2009       Accepted 24 August 2009

Copyright © 2009 Korean Diabetes Association

Abstract

Background

Although many single nucleotide polymorphisms (SNPs) of mtDNA have been found to be associated with type 2 diabetes mellitus, the results of studies using different population samples and different methods are mixed. Therefore, we conducted a genetic association study of mtDNA SNPs and type 2 diabetes mellitus in a Korean sample and compared our results with those of studies conducted in other human populations.

Methods

A total of 298 blood samples from 147 type 2 diabetic patients and 151 normal controls were surveyed for SNPs via PCR directed sequencing. Sequencing analyses were performed using the SeqMan module of the DNASTAR program. The identified SNPs were compared to previously reported SNP lists on NCBI and V-mitoSNP.

Results

A total of 24 SNPs were identified in the MT-RNR2, MR-TL1 and MT-ND1 mtDNA genes in Korean type 2 diabetes mellitus patients and normal controls. The SNPs identified in the Korean sample were not closely associated with the type 2 diabetes mellitus phenotype, a significantly different result from those previously observed in European, Chinese and Japanese samples. Additionally, a haplotype and prevalence analysis could not detect any differences between the type 2 diabetes mellitus patients and normal controls.

Conclusion

The 24 mtDNA SNPs were not associated with type 2 diabetes mellitus risk in our Korean sample. The results of the present study support the possibility that mtDNA SNPs have a differential effect on the risk of type 2 diabetes mellitus according to geographical origin.

Keywords: Mitochondrial DNA, Single nucleotide polymorphism, Type 2 diabetes mellitus

Figures and Tables

Fig. 1
Sequence results of PCR product amplified from target sequences contain SNPs on MT-RNR2 gene. The arrows indicate the variant bases. A. SNPs were observed from both T2DM and normal subjects. B. SNPs were observed from only normal subjects. SNP, single nucleotide polymorphism; T2DM, type 2 diabetes mellitus.
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Fig. 2
Sequence results of PCR product amplified from target sequences contain SNPs on MT-ND1 gene. The arrows indicate the variant bases. A. SNPs were observed from both T2DM and normal subjects. B. SNPs were observed from only T2DM subjects. C. SNPs were observed from only normal subjects. SNP, single nucleotide polymorphism; T2DM, type 2 diabetes mellitus.
kdj-33-382-g002
Fig. 3
Heteroplasmy observed from 3 individuals. The arrows indicate the variant bases, shown heteroplasmy. A. Heteroplasmy on MT-ND1 gene was observed from one T2DM patient. B. Heteroplasmy on MT-RNR2 gene was observed from two normal individuals. T2DM, type 2 diabetes mellitus.
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Table 1
Clinical characteristic of Korean T2DM patients and normal control subjects
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Data are means ± SD. BMI, body mass index; HDL, high density lipoprotein; LDL, low density lipoprotein; T2DM, type 2 diabetes mellitus.

Table 2
Identified SNPs on the MT-RNR2 gene
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*SNP previously reported to be associated with T2DM. SNP, single nucleotide polymorphism; T2DM, type 2 diabetes mellitus.

Table 3
Identified SNPs on the MT-ND1 gene
kdj-33-382-i003

*SNP previously reported to be associated with T2DM. SNP, single nucleotide polymorphism; T2DM, type 2 diabetes mellitus.

Table 4
Distributions of genotypes for the 7 SNPs identified from the Korean T2DM and normal control subjects
kdj-33-382-i004

CI, confidence internal; OR, odds ratio; SNP, single nucleotide polymorphism; T2DM, type 2 diabetes mellitus.

Table 5
Haplotype frequencies and evidence for T2DM association using 7 SNPs identified from the Korean T2DM and normal control subjects
kdj-33-382-i005

CI, confidence internal; OR, odds ratio; SNP, single nucleotide polymorphism; T2DM, type 2 diabetes mellitus.

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