Allele Summation of Diabetes Risk Genes Predicts Impaired Glucose Tolerance in Female and Obese Individuals

Επιστημονική δημοσίευση - Άρθρο Περιοδικού uoadl:3155795 10 Αναγνώσεις

Μονάδα:
Ερευνητικό υλικό ΕΚΠΑ
Τίτλος:
Allele Summation of Diabetes Risk Genes Predicts Impaired Glucose
Tolerance in Female and Obese Individuals
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Introduction: Single nucleotide polymorphisms (SNPs) in approximately 40
genes have been associated with an increased risk for type 2 diabetes
(T2D) in genome-wide association studies. It is not known whether a
similar genetic impact on the risk of prediabetes (impaired glucose
tolerance [IGT] or impaired fasting glycemia [IFG]) exists.
Methods: In our cohort of 1442 non-diabetic subjects of European origin
(normal glucose tolerance [NGT] n = 1046, isolated IFG n = 142,
isolated IGT n = 140, IFG+IGT n = 114), an impact on glucose homeostasis
has been shown for 9 SNPs in previous studies in this specific cohort.
We analyzed these SNPs (within or in the vicinity of the genes TCF7L2,
KCNJ11, HHEX, SLC30A8, WFS1, KCNQ1, MTNR1B, FTO, PPARG) for association
with prediabetes.
Results: The genetic risk load was significantly associated with the
risk for IGT (p = 0.0006) in a model including gender, age, BMI and
insulin sensitivity. To further evaluate potential confounding effects,
we stratified the population on gender, BMI and insulin sensitivity. The
association of the risk score with IGT was present in female
participants (p = 0.008), but not in male participants. The risk score
was significantly associated with IGT (p = 0.008) in subjects with a
body mass index higher than 30 kg/m(2) but not in non-obese individuals.
Furthermore, only in insulin resistant subjects a significant
association between the genetic load and the risk for IGT (p = 0.01) was
found.
Discussion: We found that T2D genetic risk alleles cause an increased
risk for IGT. This effect was not present in male, lean and insulin
sensitive subjects, suggesting a protective role of beneficial
environmental factors on the genetic risk.
Έτος δημοσίευσης:
2012
Συγγραφείς:
Linder, Katarzyna
Wagner, Robert
Hatziagelaki, Erifili and
Ketterer, Caroline
Heni, Martin
Machicao, Fausto
Stefan,
Norbert
Staiger, Harald
Haering, Hans-Ulrich
Fritsche,
Andreas
Περιοδικό:
PLOS ONE
Εκδότης:
Public Library of Science
Τόμος:
7
Αριθμός / τεύχος:
6
Επίσημο URL (Εκδότης):
DOI:
10.1371/journal.pone.0038224
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