Akt2 Gene common allelic variants in insulin resistance and the metabolic syndrome.
OBJECTIVE
Several lines of evidence indicate that glucose homeostasis may be under the control of Akt2 and it can therefore be seen as a candidate gene for human insulin resistance (IR) and related phenotypes. The aim of our study was the identification of Akt2 common allelic variants that might modulate susceptibility to IR and related metabolic abnormalities.


RESULTS
The Akt2 gene (exons, 5' and 3' regulatory regions) was re-sequenced in samples of 50 blood donors from the Gargano region. Two single nucleotide polymorphisms (SNPs) in 5' (rs11669332 and rs969531) and two in 3' (rs2304186 and C1658T) regulatory regions were exploited in an association study using 661 healthy unrelated Caucasian individuals from the same region. Individuals being homozygous for the T allele of rs11669332 (an Akt2 promoter) showed lower systolic blood pressure (p=0.04), total/HDL cholesterol ratio (p=0.02) and the metabolic syndrome score (p=0.04), while carriers of the A allele of rs969531 (in 5'-UTR) showed higher systolic blood pressure (p=0.027). The association between phenotypic traits and possible haplotypes was tested as well. However, no haplotype affecting the risk of metabolic abnormalities was found.


CONCLUSIONS
Two variants in 5' regulatory region of Akt2 gene are associated and may modulate susceptibility to IR and related metabolic abnormalities.
Tassi
Vittorio
V
Research Laboratory of Diabetology and Endocrinology, Scientific Institute Casa Sollievo della Sofferenza, Viale Padre Pio, 71013 San Giovanni Rotondo (FG), Italy. v.tassi@operapadrepio.it
Coco
Angelo
A
Padovano
Libera
L
De Bonis
Concetta
C
De Cosmo
Salvatore
S
Trischitta
Vincenzo
V
D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D000483:Alleles; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt