Genetic variability of the SUR1 promoter in relation to beta-cell function and Type II diabetes mellitus.
OBJECTIVE
We aimed to examine the promoter of SUR1 for genetic variation and to determine if variants were associated with Type II (non-insulin-dependent) diabetes mellitus or measures of beta-cell function.


METHODS
We examined 465 bp upstream of the ATG site in 46 Type II diabetic patients and 15 glucose tolerant control subjects by SSCP-heteroduplex analysis.


RESULTS
We identified an a --> t substitution 437 bp upstream of the ATG site. The allelic frequency was similar in 455 unrelated Type II diabetic patients and in 203 glucose tolerant control subjects matched for age (0.036, [95 % CI 0.019-0.053] vs 0.034 [95 % CI 0.009-0.059]; p = 0.92). Among the glucose tolerant subjects there were no differences between non-carriers (n = 189) and carriers (n = 14) of the variant in fasting values or 30 min values of plasma glucose and serum insulin during an oral glucose tolerance test. In a study of 233 glucose tolerant offspring of and spouses to Danish Caucasian Type II diabetic patients, non-carriers (n = 193) and carriers (n = 37) of the -437 a/t polymorphism did not differ in glucose or tolbutamide stimulated insulin response during an intravenous glucose tolerance test with intravenous tolbutamide injection [AUCs-insulin (0-8) min, 2290 +/- 1660 vs 2308 +/- 1935 pmol/l x min and AUCs-insulin(20-30 min), 3113 +/- 2033 vs. 3393 +/- 2830 pmol/l x min, respectively].


CONCLUSIONS
We have identified a novel a/t polymorphism of the SUR1 gene promoter which is not associated with Type II diabetes mellitus or measures of beta-cell function. Previous reported non-functional variants of SUR1 associated with Type II diabetes mellitus still need to be accounted for.
Hansen
T
T
Steno Diabetes Center, Gentofte, Denmark. toha@dadlnet.dk
Ambye
L
L
Grarup
N
N
Hansen
L
L
Echwald
S M
SM
Ferrer
J
J
Pedersen
O
O
D018528:ATP-Binding Cassette Transporters; D000328:Adult; D000368:Aged; D000483:Alleles; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying; D011401:Promoter Regions, Genetic; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D014044:Tolbutamide
C577507:ABCC8 protein, human; D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D014044:Tolbutamide