Linkage between a muscle-specific CK gene marker and V̇O(2max) in the HERITAGE family study

Purpose: We have reported a significant association between V̇O(2max) in the sedentary state and its response (Δ V̇O(max)) to an endurance training program with a muscle-specific creatine kinase (CKMM) gene polymorphism. The purpose of this study was to test the hypothesis of genetic linkage between the same CKMM marker and V̇O(2max) in the sedentary state as well as Δ V̇O(2max). Methods: Sib-pair linkage analysis was performed on 277 full sib-pairs from 98 Caucasian nuclear families of the HERITAGE Family Study. V̇O(2max) was measured during cycle ergometry tests before and after 20 wk of endurance training. The CKMM polymorphism was detected by the polymerase chain reaction and digestion with the NcoI restriction enzyme. Results: Frequencies for the rare (1170 base pairs) and common (985 + 185 base pairs) alleles were 0.32 and 0.68, respectively. No significant linkage (t = -0.02, P = 0.49) was detected between the CKMM marker and the age and sex adjusted V̇O(2max) (mL · kg^-1 · min^-1) in the sedentary state. However, after adjustment of Δ V̇(2max) for the effects of age, sex, initial V̇O(2max), and body mass, evidence for linkage between the CKMM locus and Δ V̇(2max) was suggestive (P = 0.04). Conclusion: The present results provide further support for the notion that the CKMM gene, or some gene in close linkage disequilibrium with it, may contribute to individual differences in the V̇O(2max) response to endurance training.