A common mitochondrial DNA variant is associated with insulin resistance in adult life

Mitochondrial DNA is maternally inherited. Mitochondrial DNA mutations could contribute to the excess of maternal over paternal inheritance of non-insulin-dependent diabetes mellitus (NIDDM). We therefore investigated the relationship between this variant, insulin resistance and other risk factors in a cohort which had been well characterised with respect to diabetes. Blood DNA was screened from 251 men born in Hertfordshire 1920-1930 in whom an earlier cohort study had shown that glucose tolerance was inversely related to birthweight. The 16189 variant (T--> C transition) in the first hypervariable region of mitochondrial DNA was detected using the polymerase chain reaction and restriction digestion. DNA analysis showed that 28 of the 251 men (11%) had the 16189 variant. The prevalence of the 16189 variant increased progressively with fasting insulin concentration (p < 0.01). The association was independent of age and body mass index and was present after exclusion of the patients with NIDDM or impaired glucose tolerance. We found that insulin resistance in adult life was associated with the 16189 variant. This study provides the first evidence that a frequent mitochondrial variant may contribute to the phenotype in patients with a common multifactorial disorder.

Adult, Aged, Base Sequence, Blood Glucose/metabolism, Body Composition, Body Mass Index, Cohort Studies, DNA/blood, DNA, Mitochondrial/genetics, Diabetes Mellitus, Type 2/genetics, England, Female, Genetic Variation, Genomic Imprinting, Glucose Intolerance/genetics, Glucose Tolerance Test, Humans, Insulin Resistance/genetics, Male, Patient Selection, Phenotype, Point Mutation, Polymerase Chain Reaction

10.1007/s001250050866

0012-186X

54-8

Poulton, J

cb26ba47-f06f-46ae-865e-4ae78e31e323

Brown, M S

cb784dec-96c7-4409-b082-37b600e060dd

Cooper, A

f96b8915-a2a6-4ece-a74e-5e55200646a8

Marchington, D R

9be7b300-df11-46e5-a1d5-653e622ba7bc

Phillips, D I

5183bb70-3e9e-4922-84ae-6b324fd48be6

15 January 1998

Poulton, J

cb26ba47-f06f-46ae-865e-4ae78e31e323

Brown, M S

cb784dec-96c7-4409-b082-37b600e060dd

Cooper, A

f96b8915-a2a6-4ece-a74e-5e55200646a8

Marchington, D R

9be7b300-df11-46e5-a1d5-653e622ba7bc

Phillips, D I

5183bb70-3e9e-4922-84ae-6b324fd48be6

Poulton, J, Brown, M S, Cooper, A, Marchington, D R and Phillips, D I (1998) A common mitochondrial DNA variant is associated with insulin resistance in adult life. Diabetologia, 41 (1), 54-8. (doi:10.1007/s001250050866).

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Published date: 15 January 1998

Keywords: Adult, Aged, Base Sequence, Blood Glucose/metabolism, Body Composition, Body Mass Index, Cohort Studies, DNA/blood, DNA, Mitochondrial/genetics, Diabetes Mellitus, Type 2/genetics, England, Female, Genetic Variation, Genomic Imprinting, Glucose Intolerance/genetics, Glucose Tolerance Test, Humans, Insulin Resistance/genetics, Male, Patient Selection, Phenotype, Point Mutation, Polymerase Chain Reaction