Interaction of the G protein beta 3 subunit T825 allele and the IRS-1 Arg972 variant in type 2 diabetes.
BACKGROUND
Type 2 diabetes mellitus is a common late-onset disease with a strong genetic component. It is characterized by insulin resistance which results from alterations in insulin signal transduction. The G protein beta 3 subunit 825T allele was recently found to be associated with hypertension and obesity which makes it a sensible candidate gene for type 2 diabetes.


METHODS
In a case-control study on 320 male patients and 962 male healthy controls we investigated the association of two candidate genes with diabetes, i.e. (i) the GNB3 825T allele, associated with a G protein beta 3 subunit splice variant and enhanced intracellular signal transduction, and (ii) the insulin receptor substrate-1 (IRS-1) 972Arg variant, which encodes a protein variant associated with cellular insulin resistance.


RESULTS
The GNB3 825T allele and the IRS-1 972Arg variant were significantly associated with diabetes (odds ratios for either variant 1.4 1.8). Odds ratios were 3 4 in males carrying both alleles.


CONCLUSIONS
The results document an association of a hypertension susceptibility gene with type 2 diabetes which may partially explain the frequent coexistence of both disorders.
Rosskopf
D
D
Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstr.55, D- 45147 Essen, Germany. dieter.rosskopf@uni-essen. de
Frey
U
U
Eckhardt
S
S
Schmidt
S
S
Ritz
E
E
Hofmann
S
S
Jaksch
M
M
Müller
N
N
Hüsing
J
J
Siffert
W
W
Jöcke
K H
KH
D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics*; D015398:Signal Transduction
C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D019204:GTP-Binding Proteins