Publications

40 In a case-control study, we examined the contribution of three genes related to lipid metabolism that may play a role in discriminating elite endurance athletes (EEA) from sedentary controls (SC). The EEA group included 154 males recruited on the basis that they had a VO2max > 74 ml/kg·min-1. The SC group comprised 159 unrelated sedentary males who had VO2max values below 50 ml/kg·min-1. PCR technique was used to amplify two microsatellites in the gene for the lipoprotein lipase (LPL) and the apolipoprotein AI (APOA1), respectively. A RFLP in the carnitine palmitoyl transferase II (CPT2) was typed by digestion with BstXI after PCR amplification. The results for the genotype distributions between EEA and SC are presented in the table.TableNo difference was found between EEA and SC in the distribution of genotypes or allelic frequencies. In summary, we found no evidence that the markers of these three candidate genes of endurance performance account for the difference in EEA and SC status.

BACKGROUND Weight loss protects against type 2 diabetes but is hard to maintain with behavioral modification alone. In an analysis of data from a nonrandomized, prospective, controlled study, we examined the effects of bariatric surgery on the prevention of type 2 diabetes. METHODS In this analysis, we included 1658 patients who underwent bariatric surgery and 1771 obese matched controls (with matching performed on a group, rather than individual, level). None of the participants had diabetes at baseline. Patients in the bariatric-surgery cohort underwent banding (19%), vertical banded gastroplasty (69%), or gastric bypass (12%); nonrandomized, matched, prospective controls received usual care. Participants were 37 to 60 years of age, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) was 34 or more in men and 38 or more in women. This analysis focused on the rate of incident type 2 diabetes, which was a prespecified secondary end point in the main study. At the time of this analysis (January 1, 2012), participants had been followed for up to 15 years. Despite matching, some baseline characteristics differed significantly between the groups; the baseline body weight was higher and risk factors were more pronounced in the bariatric-surgery group than in the control group. At 15 years, 36.2% of the original participants had dropped out of the study, and 30.9% had not yet reached the time for their 15-year follow-up examination. RESULTS During the follow-up period, type 2 diabetes developed in 392 participants in the control group and in 110 in the bariatric-surgery group, corresponding to incidence rates of 28.4 cases per 1000 person-years and 6.8 cases per 1000 person-years, respectively (adjusted hazard ratio with bariatric surgery, 0.17; 95% confidence interval, 0.13 to 0.21; P<0.001). The effect of bariatric surgery was influenced by the presence or absence of impaired fasting glucose (P = 0.002 for the interaction) but not by BMI (P = 0.54). Sensitivity analyses, including end-point imputations, did not change the overall conclusions. The postoperative mortality was 0.2%, and 2.8% of patients who underwent bariatric surgery required reoperation within 90 days owing to complications. CONCLUSIONS Bariatric surgery appears to be markedly more efficient than usual care in the prevention of type 2 diabetes in obese persons. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01479452.)

No abstract is provided for this article.

An association between a DNA sequence variant in the K+ inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene and elite endurance athlete status was recently reported (MSSE 35(5):S379, 2003). PURPOSE To examine the hypothesis of an association between the same KCNJ11 gene polymorphism and endurance performance status in Hispanics. METHODS DNA samples were successfully genotyped from 171 Hispanics subjects. Cases (n = 98) were long distance runners finishers in the highest 3 percentile, by age and gender, during their participation in an international marathon (42 km) race, while controls (n = 73) were subjects with severely compromised cardiorespiratory functions. The polymorphism was detected by PCR and digestion with Ban II endonuclease. RESULTS The three expected KCNJ11-BanII genotypes were observed in both genders and groups. These genotype frequencies, within each gender, were in Hardy-Weinberg equilibrium (X2, P>0.05) and not different (X2, P>0.05) different between genders. There was no gender difference (X2, P>0.05) in allelic frequencies. Chi-square analysis for the pooled data for both genders revealed significant differences in genotype (cases; TT = 8%, TC = 47%, CC = 45% and controls; TT = 28%, TC = 38%, CC = 34%; Chi-square = 7.7, df = 2, P = 0.02) and allele (Cases; T = 32%, C = 68% and Controls; T = 47%, C = 53%; Chi-square = 4.0, df = 1, P = 0.04) frequencies between the cases and controls. CONCLUSION As in previously shown (MSSE 35(5):S379, 2003) in Caucasians, an excess of the KCNJ11-BanII T allele is negatively associated with the complex phenotype of endurance performance status in Hispanics. Supported by CRC-RCMI 1P20RR11126, RCMI #G12RR03051, Comite de Fondismo: FPRA, Maraton Pacifico de Guardajara, and Maraton Popular de Madrid.

Introduction: Though cardiorespiratory fitness (CRF) is a well-established prognostic marker in older adults, the relationship between changes in CRF during early adulthood and long-term cardiovascular structure, function, and events remain unknown. Hypothesis: CRF and its change over time in young adults is associated with long-term outcome and cardiovascular disease (CVD). Methods: 4,872 American adults age 18-30 years underwent treadmill exercise testing at a baseline study visit in 1985-1986, and 2,472 individuals who underwent repeat treadmill testing 7 years later in CARDIA. Participants were followed for a median of 26.9 years, with assessment of obesity, echocardiographic left ventricular (LV) mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Incident CVD (cardiovascular death, heart failure, myocardial infarction, peripheral artery disease and stroke) and all-cause mortality were uniformly adjudicated. Results: From 4,872 individuals, 273 (5.6%) died and 193 (4%) experienced CVD events at a median 26.9 year follow-up. After full adjustment, each additional minute of baseline exercise test duration was associated with a 13% lower hazard of death (hazard ratio HR 0.87, 95% CI 0.81-0.92, P&lt;0.0001) and a 9% lower hazard of CVD (HR 0.91, 95% CI 0.84-0.98, P=0.008). Higher baseline fitness was associated with decreased risk of LV hypertrophy (P=0.009) and higher global longitudinal strain (P&lt;0.0001) at Year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by Year 7 was associated with a 20% increased hazard of death and CVD, along with a greater probability of LV hypertrophy and more impaired strain. There was no association between change in fitness and CAC. Conclusions: Higher fitness at baseline and improvement in fitness early in adulthood are favorably associated with CVD and mortality risk. Fitness and changes in fitness are associated with myocardial hypertrophy and dysfunction, but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis.

SIMONEN, R. L., L. PÉRUSSE, T. RANKINEN, T. RICE, D. C. RAO, and C. BOUCHARD. Familial aggregation of physical activity levels in the Québec family study. Med. Sci. Sports Exerc., Vol. 34, No. 7, pp. 1137–1142, 2002. Purpose Familial aggregation of physical activity phenotypes was investigated in 696 subjects from 200 families of the Quebec Family Study. The mean age of offspring and parents was 27 and 53 yr, respectively. Methods The levels of physical activity were estimated using a 3-d diary and a questionnaire dealing with physical activity during the past year. Results An ANOVA performed on the age and sex adjusted physical activity phenotypes revealed that there were 1.40–1.52 times more variation in physical activity levels between families than within families (0.001 <P < 0.0001), suggesting that physical activity levels aggregate in families. Maximal heritabilities (SEGPATH), adjusted for the degree of spouse resemblance, reached 25%, 16%, 19%, and 17% for the degree of inactivity, time spent in moderate to strenuous physical activities, total level of daily activity, and weekly time spent in the main activity during the previous year, respectively. Conclusion These results suggest that physical activity level is characterized by a significant degree of familial resemblance, and that inactivity has a slightly higher heritability level than moderate to strenuous physical activity or total physical activity phenotypes. The pattern of familial correlations suggests that shared familial environmental factors along with genetic factors are also important in accounting for the familial resemblance in physical activity level.

No abstract is provided for this article.

No abstract is provided for this article.

Five monozygotic twin pairs were submitted to a 10-week isokinetic strength training program and biochemical characteristics measured before and after training to determine the role of heredity in skeletal muscle adaptation, while 5 unrelated sedentary subjects served as control group. Experimental subjects performed twice 3 series of 5 bilateral reciprocal alternating knee flexions and extensions at a velocity of 90 °/s 5 times per week. Before and after the training period, for each subject, the peak muscular torque output was measured at the same velocity and the vastus lateralis muscle was biopsied for biochemical determinations. No significant change was observed in the control group. Training increased peak muscular torque output by 24%. The activities of hexokinase, malate dehydrogenase and 3-hydroxyacyl CoA dehydrogenase also increased significantly by 28, 26 and 38%, respectively. Interindividual variations in the response of these variables to training were noted but these were shown to be independent of the genotype. No overall effect of training was observed for oxoglutarate dehydrogenase activity (OGDH). However, changes were seen in individual pairs of twins and these were in opposite directions in some pairs compared to others, thus explaining the absence of a general training effect. Significant intrapair resemblance in the training response was present for OGDH (r = 0.76), indicating that the sensitivity to isokinetic strength training for OGDH was highly variable, not random and probably genetically determined.

The K+ inwardly rectifying channel of the subfamily J member 11 (KCNJ11) gene is widely expressed in cardiac, vascular-smooth and skeletal muscles. These tissues are highly relevant in cardiorespiratory endurance. PURPOSE to examine the possible association between a KCNJ11 gene polymorphism and elite endurance athlete (EEA) status. METHODS We examined the DNA of 184 male EEA (VO2max ≥ 75 ml/kg/min) and 113 male controls (CON; VO2max ≤ 49 ml/kg/min). Subject in both groups were matched by country of origin. Polymerase chain reaction amplification targeted a region of 267 base pairs, in codon 23, which included the polymorphic site (C→T transition; glutamate→lysine). RESULTS The three expected KCNJ11-BanII genotypes were observed in the EEA and CON. Allelic frequencies (EEA; C = 61%, T = 39% and CON; C = 50%, T = 50%) were significantly different between groups (χ2 = 6.2, df = 1, P = 0.01). Genotypic frequencies (EEA; CC = 37%, CT = 48%, TT = 15% and CON; CC = 29%, CT = 43%, TT = 28%) were also significantly different between EEA and CON (χ2 = 7.6, df = 2, P = 0.02). CONCLUSION Thse findings suggest that DNA sequence variation in the KCNJ11 gene is part of the complex genotype associated with the elite endurance athlete status. Supported by CRC-RCMI UPR-MSC Grant #1P20RR11126, RCMI Basic Sciences #G12RR03051 and MBRS-RISE R25GM61838.

Determinants of heart rate (HR) recovery after exercise are not well known, although attenuated HR recovery is associated with an increased risk of cardiovascular mortality. PURPOSe: Since acetylcholine receptor subtype M2 (CHRM2) plays a key role in cardiac chronotropic response, we tested the hypothesis that in healthy individuals the CHRM2 gene polymorphisms are associated with HR recovery one minute after the termination of maximal exercise test, both before and after endurance training. METHODS: The study population consisted of sedentary males and females (n=95, 42±5 yr) assigned either to a training (n=80) or a control group (n=15). A 2-week laboratory-controlled endurance training program included five 40-min sessions a week at 70–80% of the maximum HR. RESULTS: The HR recovery differed between the Intron 5 rs324640 genotypes at baseline (C/C −33±10, C/T −33±7 and T/T −40±1 1 beats per minute (bpm), P=0.008). Endurance training further strengthened the association: the less common C/C homozygotes showed 6 and 12 bpm lower HR recovery than the C/T heterozygotes, and the T/T homozygotes (P=0.001), respectively. A similar association was found between an A/T transversion at the 3' UTR of the CHRM2 gene and HR recovery at baseline (P=0.025) and after endurance training (P=0.005). CONCLUSIONS: These data suggest that DNA sequence variation in the CHRM2 locus is a potential modifier of HR recovery in the sedentary state, and after short-term endurance training program in healthy individuals. Supported by the Medical Council of the Finnish Academy of Science, Helsinki, Finland and the Ministry of Education, Helsinki, Finland.

No abstract is provided for this article.

KATZMARZYK, P. T., J. GAGNON, A. S. LEON, J. S. SKINNER, J. H. WILMORE, D. C. RAO, and C. BOUCHARD. Fitness, fatness, and estimated coronary heart disease risk: the HERITAGE Family Study. Med. Sci. Sports Exerc., Vol. 33, No. 4, 2001, pp. 585–590. Purpose: To determine the contributions of fatness and fitness to the estimated risk of future coronary heart disease (CHD). Methods: The sample consisted of 212 black and 411 white adult sedentary participants. Percent body fat (%BF) was measured using densitometry, whereas maximal oxygen uptake (V̇O2max) was measured on a cycle ergometer. Risk of future CHD was estimated using the revised Framingham Heart Study algorithm. Results: For fatness, the odds ratios for risk of future CHD were 1.83 and 1.70 for the moderate and high tertiles, respectively, compared with the low tertile. Similarly, the odds ratios for V̇O2max were 1.29 (NS) and 1.62, for the moderate and low tertiles, respectively. Removing V̇O2max from the full model had no effect; however, removing %BF resulted in a significantly weaker model (χ2 = 10.38, P < 0.01). Conclusion: Both fatness and fitness are important predictors of risk of future CHD, based on the Framingham index.

WOLFARTH, B., M. A. RIVERA, J-M. OPPERT, M. R. BOULAY, F. T. DIONNE, M. CHAGNON, J. GAGNON, Y. CHAGNON, L. PÉRUSSE, J. KEUL, and C. BOUCHARD. A polymorphism in the alpha2a-adrenoceptor gene and endurance athlete status. Med. Sci. Sports Exerc., Vol. 32, No. 10, pp. 1709–1712, 2000. Purpose In a case control study, we examined the allelic frequencies and genotype distributions of two restricted fragment length polymorphisms (RFLP) in the alpha-2A-adrenoceptor gene (ADRA2A) and beta-2-adrenoceptor gene (ADRB2) among elite endurance athletes (EEA) and sedentary controls (SC). Methods The EEA group included 148 Caucasian male subjects recruited on the basis that they had a V̇O2max > 74 mL O2·kg−1·min−1. The SC group comprised 149 unrelated sedentary male subjects, all Caucasians, from the Quebec Family Study. After digestion with the restriction enzymes Dra I (ADRA2A) and Ban I (ADRB2), Southern blotting and hybridization techniques were used to detect the mutations in the two ADR genes, which are encoded on chromosomes 10 (q24–26) and 5 (q31–32), respectively. Results For the Dra I ADRA2A RFLP, we observed a significant difference in genotype distributions between the two groups (P = 0.037). A higher frequency of the 6.7-kb allele was observed in the EEA group compared with the SC group (P = 0.013). No statistically significant difference was found between groups for the Ban I ADRB2 polymorphic site. Genotype frequencies for both genes in both groups were in Hardy-Weinberg equilibrium. Conclusions In summary, we found evidence that ADRA2A gene variability detected with Dra I is weakly associated with elite endurance athlete status, and we conclude that genetic variation in the ADRA2A gene or a locus in close proximity may play a role in being able to sustain the endurance training regimen necessary to attain a high level of maximal aerobic power.