Spanish genetic admixture is associated with larger Vo2 max decrement from sea level to 4,338 m in Peruvian Quechua

Quechua in the Andes may be genetically adapted to altitude and able to resist decrements in maximal O-2 consumption in hypoxia (Delta(V) over dot O-2max). This hypothesis was tested via repeated measures of (V) over dot O-2max (sea level vs. 4,338 m) in 30 men of mixed Spanish and Quechua origins. Individual genetic admixture level (% Spanish ancestry) was estimated by using ancestry-informative DNA markers. Genetic admixture explained a significant proportion of the variability in Delta(V) over dot O-2max after control for covariate effects, including sea level (V) over dot O-2 max and the decrement in arterial O-2 saturation measured at V. O2 max (DeltaSpO(2 max)) (R-2 for admixture and covariate effects similar to0.80). The genetic effect reflected a main effect of admixture on Delta(V) over dot O-2 max (P = 0.041) and an interaction between admixture and DeltaSpO(2 max) (P = 0.018). Admixture predicted Delta(V) over dot O-2 max only in subjects with a large DeltaSpO(2 max) (P = 0.031). In such subjects, Delta(V) over dot O-2 max was 12 - 18% larger in a subgroup of subjects with high vs. low Spanish ancestry, with least squares mean values (+/- SE) of 739 +/- 71 vs. 606 +/- 68 ml/min, respectively. A trend for interaction ( P = 0.095) was also noted between admixture and the decrease in ventilatory threshold at 4,338 m. As previously, admixture predicted Delta(V) over dot O-2 max only in subjects with a large decrease in ventilatory threshold. These findings suggest that the genetic effect on Delta(V) over dot O-2 max depends on a subject's aerobic fitness. Genetic effects may be more important ( or easier to detect) in athletic subjects who are more likely to show gas-exchange impairment during exercise. The results of this study are consistent with the evolutionary hypothesis and point to a better gas-exchange system in Quechua.