Altered beta-cell characteristics in impaired glucose tolerant carriers of a GAA trinucleotide repeat polymorphism in the frataxin gene.
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.
t Hart
L M
LM
Department of Molecular Cell Biology, Leiden University Medical Center, The Netherlands.
Ruige
J B
JB
Dekker
J M
JM
Stehouwer
C D
CD
Maassen
J A
JA
Heine
R J
RJ
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
D007328:Insulin; D033862:Iron-Binding Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D000096923:Frataxin