ABSTRACT
AIMS: To test for associations between type 2 diabetes mellitus (T2DM)-related traits and polymorphisms (SNPs) in the hepatocyte nuclear factor 4-alpha gene (HNF4A) in the Quebec Family Study cohort, and determine whether these associations are modulated by physical activity (PA). METHODS: Two HNF4A SNPs (rs1885088 G>A; rs745975 C>T), previously reported to be associated with T2DM, were studied in 528 non-diabetic subjects who underwent a 75g oral glucose tolerance test (OGTT). Glucose, insulin and C-peptide plasma levels, measured in the fasting state and during the OGTT, were used in the analysis. The amount (hours per week) of PA was assessed by questionnaire. RESULTS: The HNF4A rs1885088 SNP was not independently associated with T2DM-related traits, whereas the rs745975 was associated with fasting insulin, HOMA-IR and 2-h glucose levels (p<0.05 for all). Genotype by PA interactions were found for glucose homeostasis (p<0.0001) and insulin secretion (p