rs7607980

This literature review examines the influence of genetic polymorphisms on obesity development and adaptive responses to physical activity, focusing on five candidate genes: COMT (rs4680, Val158Met), DRD2 (rs1800497 Taq1A and rs1799732), FABP2 (rs1799883, Ala54Thr), FTO (rs9939609, A/T), and UCP1 (rs1800592, A-3826G). The review synthesizes molecular mechanisms, phenotypic associations, and implications for human health and training adaptations, noting that physical activity reduces the FTO genetic effect on obesity risk by 30-80% and that various polymorphisms show differential impacts on body composition and metabolic responses to exercise.

This study investigated the association between COBLL1 rs7607980 C allele and lower insulin resistance in overweight/obese children (N=878, mean age 10 years). The C allele was significantly associated with lower fasting insulin (p=0.002), lower HOMA-IR (p=0.035), and lower insulin levels 2h after oral glucose tolerance test (p=0.009), replicating previous findings in adults and demonstrating the effect early in childhood.

Three-stage exome sequencing and replication study identified three amino-acid polymorphisms associated with metabolic traits: CD300LG R82C associated with fasting HDL-cholesterol (p=7.2×10⁻⁸), and COBLL1 N939D (rs7607980, p=1.2×10⁻¹¹) and MACF1 M2290V (rs2296172, p=8.2×10⁻¹⁰) both associated with type 2 diabetes. The study involved exome sequencing of 1,974 Danish individuals with replication in 15,989 Danes and 63,896 Europeans.