title: Altered beta-cell characteristics in impaired glucose tolerant carriers of a GAA trinucleotide repeat polymorphism in the frataxin gene.
abstract: Friedreich's ataxia is associated with GAA trinucleotide repeat expansions in the frataxin gene. In the general population, these trinucleotide expansions are variable in length, and three types of expansions are seen: short, intermediate, and long repeats. Friedreich's ataxia patients are generally homozygous for the long repeats and exhibit diabetes as pronounced comorbidity. Ristow et al. recently reported an association between the intermediate-length normal allele in the frataxin gene and type 2 diabetes. We have  investigated in 94 subjects with impaired glucose tolerance (IGT) as to whether the length of the GAA trinucleotide repeat polymorphism in the frataxin gene associates with parameters reflecting beta-cell function. A hyperglycemic clamp at 10 mmol/l glucose for 3 h was used to quantitate beta-cell characteristics. Carriers of one or two intermediate repeat alleles (n = 32) had a 50% higher median first- phase insulin response to glucose than the noncarriers. Furthermore, they needed less time to reach peak insulin. An analysis of the distribution of the various repeat lengths in elderly type 2 diabetic (n = 179) and control subjects (n = 183), with the same age and ethnic background, did not provide evidence for an association of the intermediate-length repeat allele with type 2 diabetes in Dutch Caucasians.
authors: Department of Molecular Cell Biology, Leiden University Medical Center, The Netherlands.
authors: L M
authors: LM
authors: t Hart
authors: J B
authors: JB
authors: Ruige
authors: J M
authors: JM
authors: Dekker
authors: C D
authors: CD
authors: Stehouwer
authors: J A
authors: JA
authors: Maassen
authors: R J
authors: RJ
authors: Heine
mesh_terms: D000368:Aged; D000483:Alleles; D005260:Female; D018149:Glucose Intolerance / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D033862:Iron-Binding Proteins; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000502:physiology*; D000096923:Frataxin
chemical_list: D007328:Insulin; D033862:Iron-Binding Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D000096923:Frataxin