Evidence of interaction between type 2 diabetes susceptibility genes and dietary fat intake for adiposity and glucose homeostasis-related phenotypes.
OBJECTIVE
Genome-wide association studies have led to the identification of several susceptibility genes for type 2 diabetes mellitus (T2DM). The objective of this study was to test the hypothesis that the associations between single nucleotide polymorphisms (SNPs) in these genes and adiposity and glucose homeostasis-related phenotypes are influenced by dietary fat intake.


METHODS
Thirty-three SNPs in 9 T2DM genes (CDKAL1, CDKN2A/B, HHEX, HNF1B, IGF2BP2, KCNJ11, SLC30A8, TCF7L2 and WFS1) were tested in a maximum of 669 subjects from the Quebec Family Study. Subjects were measured for several adiposity indices and underwent a 75-gram oral glucose tolerance test. Total fat intake was estimated from a 3-day dietary record.


RESULTS
We observed 13 significant (p < or = 0.01) SNP-dietary fat interactions. Among them, IGF2BP2 rs4402960, alone or in interaction with dietary fat intake, influenced abdominal total fat (ATF: SNP effect, p = 0.006, interaction effect, p = 0.009) and abdominal visceral fat (AVF: SNP effect, p = 0.007, interaction effect, p = 0.01). Similarly, TCF7L2 rs12573128 alone or in interaction with dietary fat intake, influenced insulin sensitivity (SNP effect and interaction effect, p < or = 0.008) and glucose tolerance (SNP effect p < or= 0.009 and interaction effect, p < or = 0.01).


CONCLUSIONS
These results suggest that gene-dietary fat interactions may influence glucose homeostasis-related phenotypes and play an important role in determining the increased risk of diabetes associated with the T2DM susceptibility genes.
Ruchat
Stephanie-May
SM
Department of Preventive Medicine, Laval University, Québec, Canada.
Elks
Cathy E
CE
Loos
Ruth J F
RJ
Vohl
Marie-Claude
MC
Weisnagel
S John
SJ
Rankinen
Tuomo
T
Bouchard
Claude
C
Pérusse
Louis
L
D050154:Adiposity / Q000235:genetics; D000328:Adult; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D004032:Diet; D004041:Dietary Fats; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011792:Quebec; D055105:Waist Circumference
D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D005947:Glucose