The IRS1 G972R polymorphism and glomerular filtration rate in patients with type 2 diabetes of European ancestry.
BACKGROUND
In Mexican Americans, the IRS1 G972R polymorphism (rs1801278) has been associated to such a marked reduction in glomerular filtration rate (GFR) (i.e. β = -8.3 mL/min/1.73 m(2)) to be considered a major determinant of kidney function.


METHODS
This was a cross-sectional study to investigate whether a similarly strong effect can also be observed among individuals of European ancestry. We investigated a total of 3973 White patients with type 2 diabetes. Standardized serum creatinine was measured by the modified kinetic Jaffè reaction and estimated GFR (eGFR) calculated by the modification diet renal disease (MDRD) formula; rs1801278 was genotyped by TaqMan assay.


RESULTS
No significant association was observed, with R972 carriers showing only a modestly, not significant, lower eGFR level as compared with other subjects (β = -1.82 mL/min/1.73 m(2), P = 0.086).


CONCLUSIONS
Our data indicate that IRS1 G972R is not a strong determinant of GFR in diabetic patients of European ancestry as in Mexican Americans. Since we had 100% power to detect the previously reported association, the risk our finding is a false negative one is minimal.
IRCCS Casa Sollievo della Sofferenza, Clinical Unit of Endocrinology, San Giovanni Rotondo, Italy.
Salvatore
S
De Cosmo
Sabrina
S
Prudente
Olga
O
Lamacchia
Laura
L
Pucci
Daniela
D
Lucchesi
Christine
C
Mendonca
Diego
D
Bailetti
Massimiliano
M
Copetti
Fabio
F
Pellegrini
Mauro
M
Cignarelli
Giuseppe
G
Penno
Alessandro
A
Doria
Vincenzo
V
Trischitta
D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence
C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D003404:Creatinine
gene polymorphism; insulin-resistance; kidney dysfunction