KLOTHO KL‐VS Genotype is Associated with Cardiovascular Disease Risk Factors and Adaptations to Exercise Training

The KLOTHO gene has been found to affect cardiovascular disease (CVD) risk and longevity. We sought to determine if KLOTHO gene variants were associated with CVD risk factors at baseline and their responses to exercise training. Participants were sedentary, 50–75 yr old nonsmokers, BMI<37, and free of diabetes and CVD. Participants were weight and diet‐stable before initial testing and were weight‐stable during the 6‐mo, 3 d/wk exercise program (40 min/session, 70% VO 2 max). VO 2 max was measured on a treadmill, body composition via DEXA, and plasma lipoprotein‐lipids as the average of 2 fasting samples. DNA was genotyped for the KL‐VS variant via RFLP with sequencing controls. At baseline G allele carriers had 7–12% higher total and LDL‐C levels (P<0.05). With training TT homozygotes increased VO 2 max and decreased maximal exercise systolic blood pressure (SBP) more than G allele carriers (P<0.05). These data indicate that the KL‐VS G risk allele adversely affects a person's total and LDL‐C levels at baseline, as previously described. Furthermore, persons carrying the KLOTHO G risk allele had a smaller increase in VO 2 max and an increase, rather than a decrease, in maximal exercise SBP. Thus, the KLOTHO risk allele is associated with baseline CVD risk and exercise training may not reduce this risk to the same degree as in otherwise similar individuals not carrying the risk allele.