A functional promoter polymorphism of SLC2A4 is associated with aerobic endurance in a Chinese population

The G/A mutation in SLC2A4 promoter, rs5418, was investigated to assess the relationship between the SLC2A4 gene and aerobic endurance in the muscle uptake of glucose. Genotypic/allelic frequencies of rs5418 in SLC2A4 in 102 top-level long-distance runners (53 men and 49 women) were compared with those of 206 healthy controls (118 men and 88 women) from the same ethnic background (Han Chinese). The functional significance of rs5418 was analysed using the dual-luciferase reporter assay system. The A allele of SLC2A4 rs5418 was overrepresented in athletes (61.8%) compared with that in the controls (45.6%; P<0.05, power = 0.989), and the AA genotype in athletes (74.5%) was higher than that in the controls (66.0%; P<0.05, power = 0.999). The luciferase reporter vector containing the SLC2A4 promoter with rs5418-A alleles produced significantly greater relative luciferase activity (19.49 ± 4.41) than that with rs5418-G alleles (13.04 ± 4.45; P<0.05, power = 0.867). Our findings suggest that the AA genotype and A allele of SLC2A4 rs5418 were associated with top-level endurance performance in the northern Han Chinese population. The molecular mechanism was based on the functional mutation that changed the activity of the promoter, thereby affecting gene expression.