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The expression of the four and a half LIM domains 1 gene (FHL1) is increased in the muscle of individuals who show an improvement in insulin sensitivity index (SI) after 20 weeks of exercise training. The aim of the present study was to investigate associations between three FHL1 single nucleotide polymorphisms (SNPs) and variables derived from an IVGTT, both in the sedentary state and in response to exercise training, in participants in the HERITAGE Family Study.SNPs were typed using fluorescence polarisation methodology. Analyses were performed separately by sex and in black and white individuals.In black participants, no associations were found with any of the SNPs. In white women (n = 207), SNP rs9018 was associated with the disposition index (DI), which is calculated as SI generated from the MINMOD program (×10−4 min−1[μU/ml]−1) multiplied by acute insulin response to glucose (AIRg; pmol/l × 10 min), and the glucose disappearance index (Kg) training responses (p = 0.016 and p = 0.008, respectively). In white men (n = 222), all SNPs were associated with fasting glucose levels (p ≤ 0.05) and SNP rs2180062 with the insulin sensitivity index (SI) (p = 0.04) in the sedentary state. Two SNPs were associated with fasting insulin training response. Fasting insulin decreased to a greater extent in carriers of the rs2180062 C allele (p = 0.01) and rs9018 T allele (p = 0.04). With exercise training, SI (×10−4 min−1[μU/ml]−1: 0.68 ± 0.20 vs -0.77 ± 0.44, p = 0.046), DI (319 ± 123 vs -528 ± 260, p = 0.006) and Kg (per 100 min: 0.09 ± 0.04 vs -0.14 ± 0.8, p = 0.03) improved more in the C allele carriers at rs2180062 than in the T allele carriers.Fasting insulin and SI responses to exercise training were associated with DNA sequence variation in FHL1 in white men. Whether these associations exist only in white men remains to be investigated.