Relationship between mutations of mitochondrial DNA ND1 gene and type 2 diabetes

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Journal Title:
Volume , Issue 07, 2004
Key Word:
mitochondrial DNA;diabetes mellitus;gene mutation

Abstract: Background Recent studies have indicated that many mutations in mitochondrial (mt)DNA NDI gene region are related to diabetes mellitus. In this study we explored the relationship between various mtDNA ND1 gene mutations and type 2 diabetes mellitus (DM) among Chinese. Methods Using PCR restriction fragment length polymorphism (PCR-RFLP) analysis and gene sequencing, 4 spots of mtDNA (nt3243, nt3316, nt3394, nt3426) were screened in 478 diabetics and 430 non-diabetic subjects.Results In diabetic group, there were 13 carriers (2.72%)of 3316 G→A mutation,12 (2.51%) of 3394 T→C mutation and 2 (0.42%) of 3426A→G mutation. In controls, only 3394 T→C mutation was observed in 2 subjects (0.47%). There was significant difference in the frequency of 3316 and 3394 mutation between two groups (P<0.05, respectively). More subjects with mitochondrial DNA ND1 gene mutations had DM family history and greater tendency of maternal inheritance when compared to those patients without mutation in diabetic group(P<0.01). A 3426 mutation diabetic pedigree was studied, and we found 12 maternal members in the family had the same mutation. Conclusion mtDNA ND1 gene mutations at nt3316 (G→A), nt3394 (T→C) and 3426 (A→G) might contribute to the pathogenesis of DM with other genetic factors and environment factors.

  • [1]Nakagawa Y, Ikegami H, Yamato E, et al. A new mitochondrial DNA mutation associated with non-insulin-dependent diabetes mellitus. Biochem Biophys Res Commun 1995;209:664-668.
  • [2]Hirai M, Suzuki S, Onoda M, et al. Mitochondrial DNA 3394 mutation in the NADH dehydrogenase subunit 1 associated with non-insulin-dependent diabetes mellitus. Biochem Biophys Res Commun 1996;219:951-955.
  • [3]Shin CS, Kim SK, Park KS, et al. A new point mutation (3426, A to G) in mitochondrial NADH dehydrogenase gene in Korean diabetic patients which mimics 3243 mutation by restriction fragment length polymorphism pattern. Endocr J 1998;45:105-110.
  • [4]Kirby DM, Milovac T, Thorburn DR. A False-Positive Diagnosis for the Common MELAS (A3243G) Mutation Caused by a Novel Variant (A3426G) in the ND1 Gene of Mitochondria DNA. Mol Diagn 1998;3:211-215.
  • [5]Wollheim CB. Beta-cell mitochondria in the regulation of insulin secretion: a new culprit in Type Ⅱ diabetes. Diabetologia 2000;43:265-277.
  • [6]Poulton J, Macaulay V, Marching DR. Mitochondrial genetics'98 is the bottleneck cracked? Am J Hum Genet 1998,62:752-757.
  • [7]Thorns C, Widjaja A, Boeck N, et al. Maternally inherited diabetes and deafness: report of two affected German families with the A3243G mitochondrial DNA mutation. Exp Clin Endocrinol Diabetes 1998;106:384-388.
  • [8]Wallace DC. Mitochondrial diseases in man and mouse. Science 1999;283:1482-1485.
  • [9]Nakano S, Fukuda M, Hotta F, et al. Mitochondrial DNA point mutation at nucleotide pair 3316 in a Japanese family with heterogeneous phenotypes of diabetes. Endocr J 1998;45:625-630.
  • [10]Ji L, Hou X, Han X. Prevalence and clinical characteristics of mitochondrial tRNA leu (UUR) nt 3243 A→G and ND-1 gene nt 3316 G→A mutations in Chinese patients with type 2 diabetes.Chin Med J 2001;114:1205-1207.
  • [11]Zhao Q, Zhang L.Relationship between mitochondrial DNA nt3394T→C mutation in the ND1 gene region and DM. Chin J Med Genet (Chin) 2001;18:229-230.
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