The ACAA-insertion/deletion polymorphism at the 3' UTR of the IGF-II receptor gene is associated with type 2 diabetes and surrogate markers of insulin resistance.
OBJECTIVE
The IGF-II receptor gene (IGFIIR) is located at chromosome 6q26, a region that harbors a genetic marker linked to insulin-resistant traits in Mexican-Americans. In the present study conducted in Spaniards, we tested a common polymorphism in IGFIIR for association with type 2 diabetes and insulin-resistant traits.


METHODS
Case-control association study.


METHODS
One hundred and forty-five type 2 diabetic patients and 217 non-diabetic controls were genotyped for the ACAA-insertion/deletion polymorphism at the 3' UTR of IGFIIR. Phenotyping included anthropometrics and a metabolic profile, including serum lipid levels and surrogate indexes of insulin resistance whenever possible.


RESULTS
Diabetic patients were more frequently homozygous for the wild type 144 bp allele of IGFIIR compared with controls (diabetic patients 77.2%, controls 51.6%, P<0.001) suggesting a potential protective role against type 2 diabetes for the IGFIIR 140 bp variant. Carrying 140 bp alleles was associated with an odds ratio of having diabetes of 0.290 (95% confidence interval 0.109-0.770), and controls homozygous for the wild type 144 bp allele presented with lower insulin and triglyceride levels, which are proxies for insulin resistance.


CONCLUSIONS
The ACAA-insertion/deletion polymorphism at the 3' UTR of IGFIIR is associated with type 2 diabetes and influences surrogate markers of insulin resistance in non-diabetic subjects.
Villuendas
Gemma
G
Department of Endocrinology, Hospital Universitario Ramón y Cajal and Universidad de Alcalá, Carretera de Colmenar Km. 9.1, Madrid E-28034, Spain.
Botella-Carretero
José I
JI
López-Bermejo
Abel
A
Gubern
Carme
C
Ricart
Wifredo
W
Fernández-Real
José Manuel
JM
San Millán
José L
JL
Escobar-Morreale
Héctor F
HF
D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017527:Receptor, IGF Type 2 / Q000235:genetics*
D020413:3' Untranslated Regions; D005819:Genetic Markers; D017527:Receptor, IGF Type 2