Abstract 1396: Physical Activity and FTO-genotype Interact in Association With Glucose Homeostasis Change in the IRAS Cohort
Objective: to test interaction between FTO-genotype and physical activity (PA) on changes in insulin sensitivity, insulin secretion and glucose tolerance.
Methods: 183 blacks, 303 Hispanics and 356 whites, age 39 – 69 years, 56% females, were followed up for 5 years. Frequently-sampled intravenous glucose tolerance test was performed at baseline and follow-up. Insulin sensitivity (SI) and acute insulin response (AIR) were derived with MINMOD analysis. Disposition index (DI) was calculated as SI*AIR. SIDIF, AIRDIF and DIDIF were calculated by subtraction of baseline from follow-up measures. PA total energy expenditure (TEE) was estimated at baseline with a structured interview. Out of 27 genotyped FTO single nucleotide polymorphisms (SNPs), 22, 12 and 9 SNPs were selected for analysis in blacks, Hispanics and whites correspondingly based on minor allele frequency (>5%), Hardy-Weinberg equilibrium and linkage disequilibrium structure. Covariates were age, sex, study site, and baseline glucose tolerance status.
Results: in blacks, SNP rs1421085 modified the association of TEE with SIDIF (p=0.003) and DIDIF (p<0.001); in those with T:C/C:C genotype, TEE was significantly positively associated with SIDIF and DIDIF, while in those with T:T genotype, TEE was not associated with DIDIF and negatively associated with SIDIF. Also in blacks SNPs rs6499642 and rs13337696 modified the association of TEE with AIRDIF (p<0.01). In both blacks and Hispanics, there was an interaction between rs13334933 and TEE on AIRDIF (p<0.001); in G:A/A:A group, TEE was positively associated with AIRDIF, whereas in G:G group there was no association between TEE and AIRDIF. In Hispanics, rs8047395 modified the association between TEE and DIDIF (p<0.001). In those with A:A genotype, TEE was positively associated with DIDIF; in A:G/G:G group TEE was negatively associated with DIDIF. All interactions remained significant after adjustment for BMI and BMI change. There was no interaction between FTO-genotype and TEE in whites.
Conclusion: we observed modification of PA effect on SIDIF, AIRDIF and DIDIF by several markers within the first intron of FTO-gene in blacks and Hispanics but not in whites. FTO-genotype together with PA may play role in the development of type 2 diabetes.
This research has received full or partial funding support from the American Heart Association, Mid-Atlantic Affiliate (Maryland, North Carolina, South Carolina, Virginia & Washington, DC).