Role of urotensin II gene in genetic susceptibility to Type 2 diabetes mellitus in Japanese subjects.
OBJECTIVE
Urotensin II is a potent vasoactive hormone and the urotensin II gene (UTS2) is localized to 1p36-p32, one of the regions reported to show possible linkage with Type 2 diabetes in Japanese subjects. The aim of this study is to investigate a possible contribution of SNPs in the UTS2 gene to the development of Type 2 diabetes.


METHODS
We surveyed SNPs in the UTS2 gene in 152 Japanese subjects with Type 2 diabetes mellitus and two control Japanese cohorts: one consisting of 122 elderly subjects who met stringent criteria for being non-diabetic, including being older than 60 years of age with no evidence of diabetes (HbA(1c)<5.6%), and another 268 subjects with normal glucose tolerance.


RESULTS
We identified two SNPs with amino acid substitutions, designated T21M and S89N. The allele frequency of 89N was higher in Type 2 diabetic patients than in both elderly normal subjects (p=0.0018) and subjects with normal glucose tolerance (p=0.0011), whereas the allele frequency of T21M was essentially identical in these three groups. Furthermore, in the subjects with normal glucose tolerance, 89N was associated with higher insulin concentrations on oral glucose tolerance test, suggesting reduced insulin sensitivity in subjects with 89N.


CONCLUSIONS
These results strongly suggest that the S89N polymorphism in the UTS2 gene is associated with the development of Type 2 diabetes, via insulin sensitivity, in Japanese subjects.
Wenyi
Z
Z
Division of Molecular Metabolism and Diabetes, Department of Internal Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
Suzuki
S
S
Hirai
M
M
Hinokio
Y
Y
Tanizawa
Y
Y
Matsutani
A
A
Satoh
J
J
Oka
Y
Y
D000368:Aged; D017398:Alternative Splicing; D044466:Asian People / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018149:Glucose Intolerance / Q000235:genetics*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D007564:Japan; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D014579:Urotensins / Q000235:genetics*
D001786:Blood Glucose; D007328:Insulin; D014579:Urotensins; C029677:urotensin II