KCNC1 Gene Polymorphism and OV2max

0710 The K+ voltage-gated channel of the shaw-related subfamily member 1 (KCNC1) gene (11p15), encodes for a voltage-gated K+ channel that serves as an oxygen sensor in*uencing pulmonary artery smooth muscle (PASM) cells excitability in hypoxic conditions, such as high intensity physical activity. PURPOSE: We examined the hypothesis of association between a G\A transition in the KCNC1 gene and OV2max in the sedentary (SS) and trained (TS) states, as well as in response (Δ) to 20-wk endurance-training (ET). METHODS: Pre- and Post-ET VO2 was measured by progressive exercise tests on a cycle ergometer. The polymorphism was detected by PCR and digestion with MspI in 777 DNA samples from the HERITAGE Family Study (Blacks = 275 and Whites = 502). RESULTS: Genotypic distributions were in Hardy- Weinberg equilibrium. χ2 indicated that genotype frequencies were different between races (P <0.0001) but not between genders (p>0.05). ANCOVA revealed statistically significant genotype effects for SS OV2max (P = 0.04) and TS OV2max (P = 0.01) values adjusted for age, gender and body mass. In Blacks only, homozygotes for the rare A allele had significantly higher SS (2329 ± 44 mL/min) and TS OV2max (2729 ± 45 mL/min) than both GG homozygotes (SS = 2314 ± 40 mL/min; TS = 2683 ± 43 mL/min) and GA heterozygotes (SS = 2241 ± 36 mL/min; TS = 2614 ± 36 mL/min). CONCLUSIONS: These findings suggest that DNA sequence variation in the KCNC1 gene is part of the complex genotype associated with OV2max in the sedentary and trained states in Blacks, but not in Whites. Supported by several grants from NHLBI of NIH, CRC-RCMI #1P20RR11126, and RCMI #G12RR03051.