Biomedical subjects

J Gagnon

Publications and source records attributed to J Gagnon.

At least 55 records · Page 3Linked to original sources

PubMed2000

The SepOvotropin: a new ovarian peptide regulating oocyte transport in Sepia officinalis.

In the cuttlefish Sepia officinalis, the successive steps of egg laying are controlled by multiple neuropeptides. Recent experiments led us to suppose that there was possible involvement of a second regulation pathway by the release of ovarian regulatory peptides in the genital tract. Using HPLC fractionation and an in vitro biological test, a C-terminal amidated peptide modulating the motility of the Sepia officinalis oviduct was isolated from an extract of vitellogenic ovarian follicles. The mass of this peptide as determined by MALDI-TOF (1501.8 Da) and analysis by Edman degradation led to the following sequence: Pro-Lys-Asp-Ser-Met-Leu-Leu-Leu-Gln-Val-Pro-Val-Tyr-amide. The peptide mapping performed by LC/MS revealed a distribution restricted to the follicles, the full grown oocytes and the eggs. This new peptide, called SepOvotropin, modulated contractions of the whole genital tract in physiological conditions from a threshold concentration between 10(-20) and 10(-19) M, demonstrating for the first time the occurrence of a specific peptidergic control of egg-laying in cephalopods.

Amino Acid Sequence↗

PubMed2000

ILME: a waterborne pheromonal peptide released by the eggs of Sepia officinalis.

A novel tetrapeptide modulating the oviduct contractions was characterized from egg mass of Sepia officinalis. After two purification steps by rpHPLC, an apparent pure fraction containing the biological activity was submitted to MALDI-TOF analysis. The mass spectrum revealed 6 peaks of m/z 293, 505, 596, 613, 728, and 745. The tissue peptide mapping performed in LC-MS demonstrated the occurrence of the m/z 505 peptide in the follicles, the full-grown oocytes, and in the eggs. This peptide was also recovered in the seawater after the incubation of full grown oocytes or eggs, demonstrating a release in the genital tract and in the environment. Edman degradation gave the following sequence: Ileu-Leu-Met-Glu. The synthetic peptide applied to the whole genital tract triggered a cyclisation of the contractions at 10(-14) M. ILME appeared to be a chemical messenger released by the oocytes and the eggs, and was able to exert both paracrine and pheromonal activity.

Animals↗

PubMed2000

Squash trypsin inhibitors from Momordica cochinchinensis exhibit an atypical macrocyclic structure.

Three trypsin inhibitors (TIs), from the seeds of the squash Momordica cochinchinensis (MCo), have been isolated and purified using gel filtration, ion exchange chromatography, and reverse-phase HPLC. Their sequences could be determined only after proteolytic cleavages. In the case of MCoTI-I and -II, it was shown that their polypeptide backbones are cyclic, a structure that has never been described in squash TIs. They contain 34 amino acid residues with 3 disulfide bridges and measured molecular masses of 3453.0 and 3480.7, respectively. They are the largest known macrocyclic peptides containing disulfide bridges. Their sequences show strong homology to other squash TIs, suggesting a similar three-dimensional structure and an analogous mechanism of action. A model of MCoTI-II was constructed by analogy to the crystal structure of the complex between bovine trypsin and CMTI-I, indicating that the linker connecting the two termini is flexible and does not impose significant geometrical constraints. This flexibility allows an Asp-Gly peptide bond rearrangement to occur in this region, giving rise to two isoforms of MCoTI-II. Although the importance of cyclization is not clear, it might confer increased stability and resistance to proteolysis. A minor species, MCoTI-III, was also characterized as containing 30 amino acid residues with a molecular mass of 3379.6. This component possesses a linear backbone with a blocked N-terminus. MCoTIs represent interesting candidates for drug design, either by changing their specificity of inhibition or by using their structure as natural scaffolds bearing new binding activities.

Amino Acid Sequence↗

PubMed2000

Linkage and association studies of the lipoprotein lipase gene with postheparin plasma lipase activities, body fat, and plasma lipid and lipoprotein concentrations: the HERITAGE Family Study.

Lipoprotein lipase (LPL) is responsible for the hydrolysis of triglyceride (TG)-rich lipoproteins. The aims of the present study were (1) to test for potential linkages (sib-pair method) between postheparin plasma lipase (lipoprotein and hepatic lipase) activities, body fatness, plasma lipid concentrations, and LPL polymorphisms (Ser447Ter and a tetranucleotide repeat) and microsatellite markers flanking the LPL locus (D8S261 and D8S258); and (2) to investigate associations between the LPL Ser447Ter (S447X) polymorphism and these phenotypes. Data on 190 parents and 312 adult offspring from 99 Caucasian families participating in the HERITAGE Family Study were available for this study. Data were adjusted for the effects of age within sex, and lipases, lipid variables, and abdominal visceral fat were further adjusted for fat mass. A suggestive linkage was observed only between the S447X polymorphism and very-low-density (VLDL)-apolipoprotein B (apo B) (332 sib-pairs, P = .013). The S447X polymorphism was not associated with body fat phenotypes or postheparin plasma LPL (PH-LPL) activity (men, P = .19; women, P = .47). In contrast, the X447 allele carriers had lower plasma TG (men and women, P = .01), VLDL-TG (men and women, P = .01), and VLDL-apo B (men and women, P = .009). The relationships between the X447 allele and plasma TG, VLDL-TG, and VLDL-apo B in both genders were observed in obese (body mass index [BMI] > or = 30 kg/m2) but not in normal-weight (BMI < 25 kg/m2) subjects. Thus, the S447X polymorphism of the LPL gene is not associated with body fatness and postheparin plasma lipase activities. However, the obese carriers of the X447 allele have plasma TG, VLDL-TG, and plasma cholesterol/high-density lipoprotein cholesterol (HDL-C) levels equivalent to those of normal-weight sedentary adults.

Adipose Tissue↗

PubMed2000

Blood lipid response to 20 weeks of supervised exercise in a large biracial population: the HERITAGE Family Study.

We studied the effects of 20 weeks of supervised cycle-ergometer exercise on plasma lipids in 675 healthy, sedentary, normolipidemic white and black men and women aged 17 to 65 years, participating in the HERITAGE Family Study. Fasting plasma lipids were assessed twice at baseline and 24 and 72 hours after the last exercise session and adjusted for plasma volume changes. No significant differences from the mean baseline levels were observed for total, low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) cholesterol and apolipoprotein B (Apo B). A significant reduction (P < .01) from baseline levels in plasma total and VLDL triglycerides was observed only in the 24-hour posttraining specimens, reflecting a response to the last bout of exercise. High-density lipoprotein (HDL) cholesterol increased 3.6% for the combined group, primarily due to an increase in HDL2, with an associated increase in Apo A-1 (P < .001). No significant differences were noted in the HDL response by sex, race, or age. An inverse correlation (r = -.241) was observed between the increase in HDL cholesterol and change in body fat only in men, and the increase in HDL cholesterol was unrelated to the change in maximal oxygen uptake (VO2max).

Adolescent↗

PubMed2000

A genetic study of dehydroepiandrosterone sulfate measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

Familial aggregation and possible major gene effects were evaluated for the baseline serum dehydroepiandrosterone sulfate (DHEAS) level and the change in DHEAS in response to a 20-week exercise training program in a sample of 481 individuals from 99 Caucasian families who were sedentary at baseline and who participated in the HERITAGE Family Study. Baseline DHEAS levels were not normally distributed, and were therefore logarithmically transformed and adjusted for the effects of age and sex prior to genetic analysis. The DHEAS response to training was computed as the simple difference, post-training minus baseline, and was adjusted for the baseline DHEAS level, age, and sex. Maximal (genetic and familial environmental) heritabilities (using a familial correlation model) reached 58% and 30% for the baseline and the response to training, respectively. Our estimate for the baseline is generally in agreement with previous reports, suggesting that the magnitude of the familial effect underlying this phenotype in these sedentary families is similar to that in the general population. However, segregation analysis showed no evidence for a multifactorial familial component in data for either the baseline or the response to training. Rather, a major additive gene controlling the baseline was found. For the response to training in the complete sample, transmission of the major effect from parents to offspring was ambiguous, but in a subset of 56 "responsive" families (with at least 1 family member whose response to training was greater than 1 standard deviation) this major effect was Mendelian in nature. The putative major genes accounted for 50% and 33% of the variance for the baseline and the response to training, respectively. The novel finding in this study is that the baseline DHEAS level and the change in DHEAS in response to training may be influenced by major gene effects.

Adult↗

PubMed2000

Complex segregation analysis of blood pressure and heart rate measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

Complex segregation analysis of baseline resting blood pressure (BP) and heart rate (HR) and their responses to training (post-training minus baseline) were performed in a sample of 482 individuals from 99 white families who participated in the HERITAGE Family Study. Resting BP and HR were measured at baseline and after a 20-week training program. Baseline resting BP and HR were age-adjusted and age-BMI-adjusted, and the responses to training were age-adjusted and age-baseline-adjusted, within four gender-by-generation groups. This study also analyzed the responses to training in two subsets of families: (1) the so-called "high" subsample, 45 families (216 individuals) with at least one member whose baseline resting BP is in the high end of the normal BP range (the upper 95th percentile: systolic BP [SBP] > or = 135 or diastolic BP [DBP] > or = 80 mm Hg); and (2) the so-called "nonhigh" subsample, the 54 remaining families (266 individuals). Baseline resting SBP was influenced by a multifactorial component (23%), which was independent of body mass index (BMI). Baseline resting DBP was influenced by a putative recessive locus, which accounted for 31% of the variance. In addition to the major gene effect, which may impact BMI as well, baseline resting DBP was also influenced by a multifactorial component (29%). Baseline resting HR was influenced by a putative dominant locus independent of BMI, which accounted for 31% of the variance. For the responses to training, no familiality was found in the whole sample or in the nonhigh subsample. However, in the high subsample, resting SBP response to training was influenced by a putative recessive locus, which accounted for 44% of the variance. No familiality was found for resting DBP response to training. Resting HR response to training was influenced by a major effect (accounting for 35% of the variance), with an ambiguous transmission from parents to offspring.

Adolescent↗

PubMed2000

Reproducibility of resting blood pressure and heart rate measurements. The HERITAGE Family Study.

PURPOSE: This study determined the reproducibility of resting systolic and diastolic blood pressure, mean arterial pressure, and heart rate (the average of three measures/day). METHODS: The data were obtained on two separate days prior to an exercise training intervention in a sample of 822 subjects participating in the HERITAGE Family Study. The same protocol was conducted across three days in an intracenter quality control substudy, which included an additional 60 subjects. RESULTS: Reproducibility estimates included technical error, coefficient of variation within subjects, and intraclass correlation with results expressed by sex, race, age, cuff size, BMI, and %fat. Since the data were collected across four Clinical Centers, the reproducibility estimates were also computed separately for each Center. The systolic, diastolic, and mean arterial blood pressures were highly reproducible with technical errors less than 5.1 mmHg, coefficients of variation of less than 7. 0% and intraclass correlations > 0.75. The heart rates were slightly less reproducible. These results were fairly consistent across subject populations and across all four Clinical Centers. CONCLUSION: It is concluded that within subject day-to-day variations are small compared to between subject variance for resting systolic, diastolic, and mean arterial blood pressure and heart rate at each of the Clinical Centers for all of the HERITAGE Family Study data. This makes it appropriate to pool the data and analyze it for changes subsequent to endurance exercise training and to determine the possible genetic basis for these changes.

Adolescent↗

PubMed2000

Familial aggregation of amount and distribution of subcutaneous fat and their responses to exercise training in the HERITAGE family study.

OBJECTIVE: Investigate the familial aggregation of amount and distribution of subcutaneous fat and their changes in response to endurance training. RESEARCH METHODS AND PROCEDURES: A total of 483 sedentary subjects from 99 nuclear families were recruited, trained for 20 weeks of exercising on cycle ergometers, and measured before and after training for the following indicators of subcutaneous fat and fat distribution: trunk fat (TRUNK = sum of abdominal, subscapular, suprailiac, and midaxillary skinfolds), extremity fat (EXTREM = sum of biceps, triceps, thigh, and calf skinfolds), subcutaneous fat (SF8 = sum of the eight skinfolds), the trunk to extremity skinfolds ratio adjusted for SF8 (TER) and waist girth adjusted for body mass index (WAIST). The familial aggregation of the age- and sex-adjusted baseline phenotypes and their responses to training (delta) after adjustment for the baseline values was investigated using a familial correlation model. RESULTS: Significant familial aggregation was observed for all the phenotypes measured at baseline and for deltaTRUNK and deltaWAIST. Transmissibility estimates reached about 30% to 35% for TRUNK, EXTREM, and SF8 and 50% for TER and WAIST. The transmissibilities of the response phenotypes were lower, ranging from 0% for deltaWAIST to 21% for deltaTRUNK and the pattern of familial correlations suggested a greater within- than between-generation resemblance in the response. DISCUSSION: This study suggests that the amount and distribution of subcutaneous fat strongly aggregates in families, whereas the response to exercise training is characterized by a moderate and more complex pattern of familial resemblance. We conclude that familial/genetic factors are more important in determining the amount and distribution of subcutaneous fat than their responses to exercise training.

Adipose Tissue↗

PubMed2000

Evidence of pleiotropic loci for fasting insulin, total fat mass, and abdominal visceral fat in a sedentary population: the HERITAGE family study.

OBJECTIVE: To examine whether there is a major gene effect on fasting insulin and pleiotropic loci for fasting insulin, total fat mass (FM), and abdominal visceral fat (AVF). RESEARCH METHODS AND PROCEDURES: A major gene hypothesis for fasting plasma insulin levels was assessed using segregation analyses of data on 495 members in 98 normolipidemic sedentary families of white descent who participated in the HERITAGE Family Study. RESULTS: Segregation analyses were performed on insulin adjusted for age, on insulin adjusted for age and FM, and on insulin adjusted for age and AVF. Before adjustment for AVF and FM, a major gene effect on fasting insulin levels was indicated. The putative locus accounted for 54% of the variance under a recessive inheritance pattern, affecting 11% of the sample (i.e., allele frequency = 0.33). However, after adjusting for the effects of AVF or FM, neither a major effect alone nor a multifactorial component alone could be rejected, and support for a major gene was equivocal, i.e., neither the hypothesis of Mendelian tau values or that of the equal tau(s) were rejected and the equal tau model fit the data better than the Mendelian tau model. This pattern (i.e., major gene evidence for insulin before but not after adjustment for AVF or FM) suggests that there is a putative locus with pleiotropic effects on both insulin and FM and another pleiotropic locus for both insulin and AVF. DISCUSSION: Although these data do not directly support an additional major gene for insulin independent of AVF and FM, such support cannot be ruled out because there is still a significant major effect on FM- or AVF-adjusted insulin (albeit the Mendelian nature of this effect is ambiguous).

Abdomen↗

PubMed2000

A genetic study of sex hormone--binding globulin measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

Familial aggregation and a major gene effect were assessed for baseline serum sex hormone-binding globulin (SHBG) levels and the response (post-training minus baseline) to a 20-week endurance training program in a selected sample of 428 non-obese nonhypertensive individuals from 99 white families who were sedentary at baseline in the HERITAGE Family Study. Baseline SHBG levels were not normally distributed, and were therefore logarithmically transformed prior to genetic analyses. In a sample without postmenopausal mothers, maximal (genetic and familial environmental) heritabilities were 50% averaged across sexes, 73% in men, 50% in women, and 31% in men versus women for the age-body mass index (BMI)-adjusted baseline. The estimate reached 64% when the baseline was further adjusted for the effects of estradiol, fasting insulin, and testosterone levels. For the response to training, no sex difference was found and the heritability reached about 25% to 32%. Segregation analysis was separately performed in the whole sample and in the sample without postmenopausal mothers. In addition to a multifactorial effect for both the baseline and the response to training, a major effect for the baseline appeared to be familial environmental in origin, whereas a major effect for the response to training was Mendelian in nature. The major gene effect for the response to training in the whole sample was undetectable in the sample without postmenopausal mothers, and it is therefore possible that the postmenopausal mothers, characterized by decreased sex hormones with or without estrogen replacement therapy for menopause, produced some confounding effects. In addition, the reduced sample size might also be a plausible candidate explanation. The novel finding in this study is that baseline SHBG levels and the response to training were influenced by a multifactorial effect with sex difference for the baseline. The response to training appeared to be additionally influenced by a single recessive locus that is independent of baseline SHBG levels.

Adult↗

PubMed2000

Familial aggregation of stroke volume and cardiac output during submaximal exercise: the HERITAGE Family Study.

Familial aggregation of stroke volume (SV) and cardiac output (Qc by CO2 rebreathing) at 50 Watts (W) and 60 % of maximal oxygen uptake (VO2max) as well as their changes in response to a 20-week endurance exercise training program was assessed in 99 Caucasian families who participated in the HERITAGE Family Study. In order to interpret familial influences independent of effects of age, sex, and body size (indexed by body surface area here), SV and Qc levels were adjusted for these primary parameters prior to genetic analysis within four sex-by-generation groups (the responses to training were additionally adjusted for their baseline values). Maximal heritabilities for baseline SV, Qc, and their changes in response to training during the two stages of submaximal exercise were estimated using a familial correlation model. At 50W, maximal heritabilities reached 41% and 42% for baseline SV and Qc, respectively, and were 29% and 38% for the respective responses to training. At 60% of VO2max, maximal heritabilities reached 46 % for baseline SV and Qc, and were 24% and 30% for the respective responses to training. Generally there were no meaningful differences between the maximal heritabilities at 50 W and 60% of VO2max. However, the maximal heritabilities for the baseline were slightly higher than the estimates for the changes in response to training. Based upon results arising from these non-obese, non-hypertensive, and sedentary families, we found that SV and Qc at 50 W and 60% of VO2max as well as their changes in response to the 20-week endurance exercise training were moderately heritable. Not only genetic determinants but also familial non-genetic factors might attribute to the observed patterns of familial aggregation of SV and Qc during submaximal exercise in the present study.

Adult↗

PubMed2000

Adaptation to a standardized training program and changes in fitness in a large, heterogeneous population: the HERITAGE Family Study.

PURPOSE: This paper describes the variations in response to a standardized, computer-controlled training program. METHODS: Steady-state heart rate (HR) and oxygen intake (VO2) of 614 healthy, sedentary men and women aged 16-65 yr were measured during three cycle ergometer exercise tests. The HR associated with 55, 65, 70, and 75% of each subject's pretraining VO2max was used to prescribe exercise intensity. Subjects exercised three times a week, beginning at a HR associated with 55% VO2max for 30 min. Duration and intensity was gradually increased over 20 wk of training. The duration and HR of each training session were controlled by a computer. RESULTS: Using the linear relationship between HR, VO2 and power output (PO), PO were predicted for each of 60 training sessions at the respective programmed HR. The average ratio of the actual training HR to programmed HR was 0.99. It was hypothesized that participants whose actual training PO exceeded their predicted PO would improve VO2max more than those whose actual PO was less than their predicted PO. Using the ratio of actual/predicted PO determined after the training was over, participants were arbitrarily assigned to three groups: 128 participants had low (LO) ratios (0.65-0.84), 408 had average (AV) ratios (0.85-1.14), and 78 had high (HI) ratios (1.15-1.34). Secondary analysis showed that the training program significantly increased mean VO2max of all three groups. Those who had a smaller increase in training PO (LO) had significantly less increase in VO2max than those with larger increases in PO (HI). CONCLUSION: People who exercise at a HR associated with the same %VO2max can vary substantially in their training PO, in their rate of increase in PO over a 20-wk training program, and in improvement of their VO2max.

Adaptation, Physiological↗

PubMed2000

Familiality of triglyceride and LPL response to exercise training: the HERITAGE study.

PURPOSE: The main purpose of the present investigation was to test whether and to what extent familial/genetic factors are involved in the changes of postheparin lipoprotein lipase (deltaPH-LPL) activity and triglyceride (deltaTG) levels in response to exercise training. Additional hypotheses were also tested as to whether there were familial/genetic factors shared by baseline and the corresponding response to exercise training (i.e., by baseline triglyceride (TG(B)) and deltaTG and by baseline postheparin lipoprotein lipase (PH-LPL(B)) and deltaPH-LPL activity). METHODS: Serum TG and PH-LPL were measured in 459 subjects from 99 sedentary Caucasian families of the HERITAGE Family study before (baseline) and after completing a 20 wk (3 times per week) exercise training protocol. The training protocol had a target intensity of 75% of the heart rate associated with baseline VO2max during the last 6 wk. PH-LPL activity was measured in the study subjects. Both univariate and bivariate familial correlation analyses were applied to the baseline and response data. RESULTS: The maximal heritabilities for deltaTG and deltaPH-LPL activity were 22% and 15%, respectively. There were no common familial factors for TG(B) and deltaTG, nor were there any for PH-LPL(B) and deltaPH-LPL. However, we found that there were common familial factors underlying deltaTG and deltaPH-LPL; these familial factors seemed to differ across sex and generation groups. CONCLUSION: Although there were no common familial factors underlying the covariation between the baseline triglyceride and PH-LPL activity and the corresponding responses to exercise training (i.e., TG(B) with deltaTG or PH-LPL(B) with deltaPH-LPL), the deltaTG and deltaPH-LPL covariation apparently share some common familial determinants.

Adolescent↗

PubMed2000

A polymorphism in the alpha2a-adrenoceptor gene and endurance athlete status.

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 VO2max > 74 mL O2 x kg(-1) x 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.

Alleles↗

PubMed2000

AGT M235T and ACE ID polymorphisms and exercise blood pressure in the HERITAGE Family Study.

We investigated the association between angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) gene polymorphisms and exercise training responses of resting and exercise blood pressure (BP). BP at rest and during submaximal (50 watts) and maximal exercise tests was measured before and after 20 wk of endurance training in 476 sedentary normotensive Caucasian subjects from 99 families. AGT M235T and ACE insertion/deletion polymorphisms were typed with PCR-based methods. Men carrying the AGT MM and MT genotypes showed 3. 7 +/- 0.6 and 3.2 +/- 0.5 (SE) mmHg reductions, respectively, in diastolic BP at 50 watts (DBP(50)), whereas, in the TT homozygotes, the decrease was 0.4 +/- 1.0 mmHg (P = 0.016 for trend, adjusted for age, body mass index, and baseline DBP(50)). Men with the ACE DD genotype showed a slightly greater decrease in DBP(50) (4.4 +/- 0.6 mmHg) than the II and ID genotypes (2.8 +/- 0.7 and 2.4 +/- 0.5 mmHg, respectively, P = 0.050). Furthermore, a significant (P = 0.022) interaction effect between the AGT and ACE genes was noted for DBP(50); the AGT TT homozygotes carrying the ACE D allele showed no response to training. Men with the AGT TT genotype had greater (P = 0.007) diastolic BP (DBP) response to acute maximal exercise at baseline. However, the difference disappeared after the training period. No associations were found in women. These data suggest that, in men, the genetic variation in the AGT locus modifies the responsiveness of submaximal exercise DBP to endurance training, and interactions between the AGT and ACE loci can alter this response.

Adult↗

PubMed2000

The Na(+)-K(+)-ATPase alpha2 gene and trainability of cardiorespiratory endurance: the HERITAGE family study.

The Na(+)-K(+)-ATPase plays an important role in the maintenance of electrolyte balance in the working muscle and thus may contribute to endurance performance. This study aimed to investigate the associations between genetic variants at the Na(+)-K(+)-ATPase alpha2 locus and the response (Delta) of maximal oxygen consumption (VO(2 max)) and maximal power output (W(max)) to 20 wk of endurance training in 472 sedentary Caucasian subjects from 99 families. VO(2 max) and W(max) were measured during two maximal cycle ergometer exercise tests before and again after the training program, and restriction fragment length polymorphisms at the Na(+)-K(+)-ATPase alpha2 (exons 1 and 21-22 with Bgl II) gene were typed. Sibling-pair linkage analysis revealed marginal evidence for linkage between the alpha2 haplotype and DeltaVO(2 max) (P = 0.054) and stronger linkages between the alpha2 exon 21-22 marker (P = 0.005) and alpha2 haplotype (P = 0.003) and DeltaW(max). In the whole cohort, DeltaVO(2 max) in the 3.3-kb homozygotes of the exon 1 marker (n = 5) was 41% lower than in the 8.0/3.3-kb heterozygotes (n = 87) and 48% lower than in the 8.0-kb homozygotes (n = 380; P = 0.018, adjusted for age, gender, baseline VO(2 max), and body weight). Among offspring, 10.5/10.5-kb homozygotes (n = 14) of the exon 21-22 marker showed a 571 +/- 56 (SE) ml O(2)/min increase in VO(2 max), whereas the increases in the 10.5/4.3-kb (n = 93) and 4.3/4.3-kb (n = 187) genotypes were 442 +/- 22 and 410 +/- 15 ml O(2)/min, respectively (P = 0.017). These data suggest that genetic variation at the Na(+)-K(+)-ATPase alpha2 locus influences the trainability of VO(2 max) in sedentary Caucasian subjects.

Adaptation, Physiological↗

PubMed2000

Genomic scan for maximal oxygen uptake and its response to training in the HERITAGE Family Study.

This study aimed to identify human genomic regions that are linked to maximal oxygen uptake (VO(2 max)) in sedentary individuals or to the responsiveness of VO(2 max) to a standardized endurance training program. The results of a genomic scan based on 289 polymorphic markers covering all 22 pairs of autosomes performed on the Caucasian families of the HERITAGE Family Study are presented. The mean spacing of the markers was 11 cM, and a total of 99 families and 415 pairs of siblings were available for the study. VO(2 max) in the sedentary state was adjusted for the effects of age, sex, body mass, fat mass, and fat-free mass, whereas the VO(2 max) response was adjusted for age and baseline level of the phenotype. Two analytic strategies were used: a single-point linkage procedure using all available pairs of siblings (SIBPAL) and a multipoint variance components approach using all the family data (SEGPATH). Results indicate that linkages at P values of 0.01 and better are observed with markers on 4q, 8q, 11p, and 14q for VO(2 max) before training and with markers on 1p, 2p, 4q, 6p, and 11p for the change in VO(2 max) in response to a 20-wk standardized endurance training program. These chromosomal regions harbor many genes that may qualify as candidate genes for these quantitative traits. They should be investigated in this and other cohorts.

Adolescent↗