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Biomedical subjects

Stephen M Roth

Publications and source records attributed to Stephen M Roth.

At least 19 recordsLinked to original sources
PubMed2006

AMPD1 gene polymorphism and the vasodilatory response to ischemia.

Peripheral vasculature resistance can play an important role in affecting blood pressure and the development of cardiovascular disease. A better understanding of the genes that encode vasodilators, such as adenosine, will provide insight into the mechanisms underlying cardiovascular disease. We tested whether the adenosine monophosphate deaminase-1 (AMPD1) C34T gene polymorphism was associated with the vasodilatory response to ischemia in Caucasian females aged 18-35 years. Blood samples (n = 58) were analyzed for the C34T variant and resulted in the following genotype groups: CC (n = 45) and CT (n = 13). Mean blood pressure (MBP), heart rate, and forearm blood flow (FBF) measured by venous occlusion plethysmography were measured at baseline and at 1 (peak FBF), 2 and 3 min of vasodilation during reactive hyperemia following 5 min of arm ischemia. To control for interindividual variability in baseline FBF and forearm vascular resistance (FVR) the percent change in FBF and FVR were calculated for each min. The percent decrease in FVR was significantly greater in the CT compared to the CC genotype group (-40+/-4% vs. -24+/-3%, P = 0.01) during the 2nd min of reactive hyperemia. The percent increase in FBF tended to be greater in the CT compared to the CC genotype group (+69+/-9% vs. +42+/-9%, P = 0.07) during the 2nd min of reactive hyperemia after adjustment for percent body fat. Consistent with previous findings of increased production of adenosine during exercise in individuals carrying a T allele, our findings suggest that the AMPD1 C34T polymorphism is associated with vasodilatory response to ischemia in the peripheral vasculature because individuals with the T allele had a greater vasodilatory response to ischemia.

AMP Deaminase↗
PubMed2006

Hemostatic response to postprandial lipemia before and after exercise training.

Chronic hypertriglyceridemia is thought to be atherogenic and is associated with an elevated thrombotic potential, both of which may be improved with aerobic exercise training. Eight subjects were tested for aerobic capacity, body composition, and postprandial lipemia (PPL), followed by 6 mo of exercise training and final testing. Blood samples were obtained for measurement of free fatty acid (FFA), triglycerides (TG), insulin (Ins), and glucose (Glu). Hemostatic variables including factor VII activity (FVIIa), tissue factor pathway inhibitor-factor Xa complex (TFPI/Xa), and plasminogen activator inhibitor-1 (PAI-1) antigen/activity as well as leukocyte tumor necrosis factor-alpha (TNF-alpha) gene expression were determined among four subjects. We found that the exercise training was of sufficient intensity to increase aerobic capacity (P < 0.0001) and improve body composition (P = 0.04). There were no differences between tests among PPL responses of FFA, TG, Ins, or Glu; however, the mean TG response and fat oxidation rate improved. PAI-1 antigen/activity, FVIIa, TFPI/Xa, and TNF-alpha gene expression were all improved after exercise training after adjusting for confounders. We conclude that aerobic exercise training reduces the potential for coagulation, improves fibrinolytic potential, and reduces leukocyte TNF-alpha gene expression after the ingestion of a high-fat meal.

Aged↗
PubMed2006

Age and sex affect human muscle fibre adaptations to heavy-resistance strength training.

This study assessed age and sex effects on muscle fibre adaptations to heavy-resistance strength training (ST). Twenty-two young men and women (20-30 years old) and 18 older men and women (65-75 years old) completed 9 weeks of heavy-resistance knee extension exercises with the dominant leg 3 days week(-1); the non-dominant leg served as a within-subject, untrained control. Bilateral vastus lateralis muscle biopsies were obtained before and after ST for analysis of type I, IIa and IIx muscle fibre cross-sectional area (CSA) and fibre type distribution. One-repetition maximum (1-RM) strength was also assessed before and after ST. ST resulted in increased CSA of type I, IIa and IIx muscle fibres in the trained leg of young men, type I and IIa fibres in young women, type IIa fibres in older men, and type IIx fibres in older women (all P<0.05). Analysis of fibre type distribution revealed a significant increase in the percentage of type I fibres (P<0.05) along with a decrease in type IIx fibres (P=0.054) after ST only in young women. There were no significant changes in muscle fibre CSA or fibre type distribution in the untrained leg for any group. All groups displayed significant increases in 1-RM (27-39%; all P<0.01). In summary, ST led to significant increases in 1-RM and type II fibre CSA in all groups; however, age and sex influence specific muscle fibre subtype responses to ST.

Adaptation, Physiological↗
PubMed2006

Inflammatory factors in age-related muscle wasting.

PURPOSE OF REVIEW: This review focuses on recent evidence pointing to the importance of inflammatory factors in the onset and progression of age-related muscle wasting, also known as sarcopenia, and discusses critical areas of uncertainty within the literature that require further development in order to identify novel therapeutics. RECENT FINDINGS: The research performed in recent years has only strengthened the evidence that inflammatory factors are important in the progression of a catabolic state in muscle wasting. Interactions among various inflammatory cytokines and anabolic factors have been observed, with the balance skewed in favor of catabolism in sarcopenia. Adiposity appears to play an important role in the inflammatory process and possibly the onset of sarcopenia. Inflammatory factors are likely to play an important role in the increased activity of the ubiquitin proteasome, which we argue should be a primary target for the development of molecular therapeutics. SUMMARY: Future research will need to delve into the molecular interactions that link inflammatory factors and the imbalance between muscle anabolism and catabolism that develops with aging. Identification of specific pathways of importance to sarcopenia will have relevance to a wide range of wasting disorders.

Aging↗
PubMed2006

The human gene map for performance and health-related fitness phenotypes: the 2005 update.

The current review presents the 2005 update of the human gene map for physical performance and health-related fitness phenotypes. It is based on peer-reviewed papers published by the end of 2005. The genes and markers with evidence of association or linkage with a performance or fitness phenotype in sedentary or active people, in adaptation to acute exercise, or for training-induced changes are positioned on the genetic map of all autosomes and the X chromosome. Negative studies are reviewed, but a gene or locus must be supported by at least one positive study before being inserted on the map. By the end of 2000, in the early version of the gene map, 29 loci were depicted. In contrast, the 2005 human gene map for physical performance and health-related phenotypes includes 165 autosomal gene entries and QTL, plus five others on the X chromosome. Moreover, there are 17 mitochondrial genes in which sequence variants have been shown to influence relevant fitness and performance phenotypes. Thus, the map is growing in complexity. Unfortunately, progress is slow in the field of genetics of fitness and performance, primarily because the number of laboratories and scientists focused on the role of genes and sequence variations in exercise-related traits continues to be quite limited.

Anthropometry↗
PubMed2006

Identification of a novel mutation combination in factor XIII deficiency: genetic update to the first reported case in the United States.

A 1967 report described the first known case of congenital factor XIII (FXIII) deficiency in the United States in a male patient with a severe hemorrhagic disorder. The patient's family presented no symptoms of the disorder, but the members were found to have half the normal FXIII activity. Although the molecular basis of the disorder could not be evaluated at the time, the results suggested an autosomal recessive inherited disorder. We sequenced all of the exons and the flanking regions in the genes for the FXIII A and B subunits of the patient, his family, and 18 unrelated individuals. We report the novel combination of an Arg-to-Cys mutation at codon 78 and a G-to-C mutation at the intron 5/exon 6 splice junction in the patient's FXIIIA gene. The missense-splice junction mutation combination appears to have caused the patient's FXIIIA deficiency, because the remaining family members, who present no symptoms and have no clinical diagnoses of FXIII deficiency, have one or the other of the 2 mutations but not both. Additionally, the 18 unrelated individuals are homozygous wild type at these loci. The molecular consequences of these mutations appear to be an abnormality in protein conformation or folding and/or a reduced production of messenger RNA transcripts of varying length that likely result in a nonfunctional, unstable FXIII protein.

Adult↗
PubMed2005

DNA sequence variation in the promoter region of the VEGF gene impacts VEGF gene expression and maximal oxygen consumption.

In its role as an endothelial cell proliferation and migration factor, vascular endothelial growth factor (VEGF) can affect peripheral circulation and therefore impact maximal oxygen consumption (Vo2 max). Because of the role of VEGF, and because variation in the VEGF gene has the ability to alter VEGF gene expression and VEGF protein level, we hypothesized that VEGF gene polymorphisms are related to VEGF gene expression in human myoblasts and Vo2 max before and after aerobic exercise training. We analyzed the effects of the VEGF -2578/-1154/-634 promoter region haplotype on VEGF gene expression by using a luciferase reporter assay in cultured human myoblasts and found that the AAG and CGC haplotypes resulted in significantly higher hypoxia-stimulated VEGF gene expression than the AGG and CGG haplotypes. Consistent with these results, we found that individuals with at least one copy of the AAG or CGC haplotype had higher Vo2 max before and after aerobic exercise training than did subjects with only the AGG and/or CGG haplotype. In conclusion, we found that VEGF -2578/-1154/-634 haplotype impacts VEGF gene expression in human myoblasts and is associated with Vo2 max. These results have potential implications for aerobic exercise training and may prove relevant in the study of pathological conditions that can be affected by angiogenesis, such as coronary artery disease and peripheral artery disease.

Aged↗
PubMed2005

Vitamin D receptor FokI genotype influences bone mineral density response to strength training, but not aerobic training.

To determine the influence of the vitamin D receptor (VDR) gene FokI and BsmI genotype on bone mineral density response to two exercise training modalities, 206 healthy men and women (50-81 years old) were studied before and after approximately 5-6 months of either aerobic exercise training (AT) or strength training (ST). A totla of 123 subjects completed AT (51 men, 72 women) and 83 subjects completed ST (40 men, 43 women). DNA was extracted from blood samples of all subjects and genotyping was performed at the VDR FokI and BsmI locus to determine its association to training response. Total body, greater trochanter and femoral neck bone mineral density (BMD) were measured before and after both training programmes using dual-energy X-ray absorptiometry. VDR BsmI genotype was not significantly related to BMD at baseline or after ST or AT. However, VDR FokI genotype was significantly related to ST- but not AT-induced changes in femoral neck BMD (P < 0.05). The heterozygotes (Ff) in the ST group approached a significantly greater increase in femoral neck BMD (P = 0.058) compared to f homozygotes. There were no significant genotype relationships in the AT group. These data indicate that VDR FokI genotype may influence femoral neck BMD response to ST, but not AT.

Absorptiometry, Photon↗
PubMed2005

Blood pressure response to strength training may be influenced by angiotensinogen A-20C and angiotensin II type I receptor A1166C genotypes in older men and women.

OBJECTIVES: To determine the influence of angiotensinogen (AGT) A-20C, M235 T, and angiotensin II type 1 receptor (AGTR1) A1166C genotypes on resting blood pressure (BP) response to strength training (ST) in older men and women. DESIGN: Prospective intervention study with retrospective genotyping. SETTING: University of Maryland Exercise Physiology Laboratory. PARTICIPANTS: Seventy sedentary, healthy older men (n=34) and women (n=36). INTERVENTION: Approximately 23 weeks of ST performed 3 days per week. MEASUREMENTS: Resting BP was measured on six separate occasions before and after ST for each subject. AGT and AGTR1 genotyping was performed retrospectively from each subject's genomic deoxyribonucleic acid. RESULTS: Systolic BP decreased in C-allele carriers at the AGT A-20C locus with ST (122+/-1 to 116+/-2 mmHg, P<.05), which was significantly greater than the decrease in the A homozygotes (126+/-1 to 123+/-1 mmHg, P<.05). At the AGTR1 A1166C locus, diastolic BP decreased to a greater extent in the C-allele carriers (76+/-1 to 70+/-2 mmHg, P<.05) than in the A homozygotes (75+/-1 to 72+/-1 mmHg, P<.05). CONCLUSION: The AGT A-20C and AGTR1 A1166C genotypes may influence resting BP response to ST, such that C-allele carriers at each of these loci reduce their resting BP in response to ST to a greater extent than A homozygotes.

Aged↗
PubMed2005

Muscle strength response to strength training is influenced by insulin-like growth factor 1 genotype in older adults.

Strength training (ST) is considered an intervention of choice for the prevention and treatment of sarcopenia. Reports in the literature have suggested that the insulin-like growth factor I protein (IGF-I) plays a major role in ST-induced skeletal muscle hypertrophy and strength improvements. A microsatellite repeat in the promoter region of the IGF1 gene has been associated with IGF-I blood levels and phenotypes related to IGF-I in adult men and women. To examine the influence of this polymorphism on muscle hypertrophic and strength responses to ST, we studied 67 Caucasian men and women before and after a 10-wk single-leg knee-extension ST program. One repetition maximum strength, muscle volume via computed tomography, and muscle quality were assessed at baseline and after 10 wk of training. The IGF1 repeat promoter polymorphism and three single-nucleotide polymorphisms were genotyped. For the promoter polymorphism, subjects were grouped as homozygous for the 192 allele, heterozygous, or noncarriers of the 192 allele. After 10 wk of training, 1-repetition maximum, muscle volume, and muscle quality increased significantly for all groups combined (P < 0.001). However, carriers of the 192 allele gained significantly more strength with ST than noncarriers of the 192 allele (P = 0.02). There was also a nonsignificant trend for a greater increase in muscle volume in 192 carriers than noncarriers (P = 0.08). No significant associations were observed for the other polymorphisms studied. Thus these data suggest that the IGF1 promoter polymorphism may influence the strength response to ST. Larger sample sizes should be used in future studies to verify these results.

Aged↗
PubMed2005

The human gene map for performance and health-related fitness phenotypes: the 2004 update.

We began this series in 2000 with the aim of making available in an easily accessible format all the advances on the genetic basis of a large family of exercise-related traits. The current review presents the 2004 update of the human gene map for physical performance and health-related fitness phenotypes. It is based on peer-reviewed papers published by the end of 2004. The genes and markers with evidence of association or linkage with a performance or fitness phenotype in sedentary or active people, in adaptation to acute exercise, or for training-induced changes are positioned on the genetic map of all autosomes and the X chromosome. Negative studies are reviewed but a gene or locus must be supported by at least one positive study before being inserted on the map. One new feature is that we have incorporated the genes whose sequence variants have been associated with either the level of physical activity or indicators of sedentarism. By the end of 2000, in the early version of the gene map, 29 loci were depicted. In contrast, the 2004 human gene map for physical performance and health-related phenotypes includes 140 autosomal gene entries and quantitative trait loci, plus four on the X chromosome. Moreover, there are 16 mitochondrial genes in which sequence variants have been shown to influence relevant fitness and performance phenotypes. Thus, the map is growing in complexity and progress is being made. The number of laboratories and scientists concerned by the role of genes and sequence variations in exercise-related traits is rising. But exercise science and sports medicine is generally lagging behind in terms of utilizing the advances in genetic and genomic technologies.

Anthropometry↗
PubMed2004

Androgen receptor CAG repeat polymorphism is associated with fat-free mass in men.

The human androgen receptor (AR) gene contains a CAG (glutamine) repeat polymorphism in exon 1 that is inversely associated with transcriptional activity of the AR. We studied the association of AR CAG repeat length, fat-free mass (FFM), and testosterone in two independent cohorts: 294 Caucasian men, aged 55-93 yr, from the Study of Osteoporotic Risk in Men (STORM), and 202 Caucasian volunteers (112 men and 90 women), aged 19-90 yr, from the Baltimore Longitudinal Study of Aging (BLSA). Subjects were genotyped to determine the number of AR CAG repeats and grouped as carrying either < 22 or > or =22 repeats. Whole body soft tissue composition was measured by dual-energy X-ray absorptiometry. Men with greater CAG repeat number exhibited significantly greater total FFM than those with fewer CAG repeats in both cohorts (STORM: 59.2 +/- 0.3 vs. 58.0 +/- 0.4 kg, P = 0.02; BLSA: 57.2 +/- 1.1 vs. 53.8 +/- 1.1 kg, P = 0.04). Similar results were observed for total FFM normalized to height. No differences were seen in women in the BLSA cohort. In the BLSA cohort, serum testosterone levels were higher in subjects with greater repeat number (P = 0.003). This same pattern approached significance in the STORM cohort (P = 0.07). In conclusion, the androgen receptor CAG repeat polymorphism is associated with FFM in men in two independent cohorts. Additional studies are needed to confirm this observation and to clarify the mechanisms involved.

Adipose Tissue↗
PubMed2004

Insulin-like growth factor-2 genotype, fat-free mass, and muscle performance across the adult life span.

The influence of insulin-like growth factor-2 (IGF2) genotype on total body fat-free mass (FFM), muscle strength, and sustained power (SP) was evaluated repeatedly at approximately 2-yr intervals in two cohorts from the Baltimore Longitudinal Study of Aging. Cohort 1 was comprised of 94 men tested for isometric grip strength and SP. Cohort 2 was comprised of 246 men and 239 women tested for total body FFM and isokinetic peak torque. Subjects were retrospectively genotyped for the IGF2 gene's ApaI polymorphism. Differences between genotype groups for total FFM, strength, and SP at first visit, at peak age (35 yr), at age 65, and across the adult age span were analyzed using either two-sample t-tests or mixed-effects models, depending on the specific comparisons made. Isokinetic arm strength at the time of first visit was lower in A/A men than in G/G men (P < 0.05). Compared with G/G women, A/A women had lower total body FFM, lower isokinetic arm and leg strength at the time of first visit, and lower values at age 35 (all P < 0.05) for these muscle phenotypes. Furthermore, this difference between the genotype groups was maintained at age 65 and across the adult age span (P < 0.05). No genotype-associated differences in rates of loss of grip strength or SP were found in cohort 1. These results from cohort 2 support the hypothesis that variation within a gene known to influence developing muscle affects muscle mass and muscle function in later life.

Adult↗
PubMed2004

Ciliary neurotrophic factor (CNTF) genotype and body composition.

Exogenous ciliary neurotrophic factor (CNTF) administration causes significant weight loss in both humans and animal models, but the effects of endogenous CNTF and the CNTF null allele on body composition are not fully understood. A recent study in a European cohort demonstrated a significantly higher body weight and body mass index (BMI) in older males homozygous for the CNTF null allele (A/A genotype). We sought to replicate these findings in three cohorts: the Baltimore Longitudinal Study on Aging (BLSA) consisting of 422 adult men and women (19-90 years); the Study of Osteoporotic Risk in Men (STORM) consisting of 333 older men (50-84 years); and a third sample obtained by combining older males aged 59-73 years from the BLSA and STORM cohorts (n=286). In contrast to the European study, we were unable to detect a significant association between CNTF genotype and body weight in the BLSA (P=0.49), the STORM (P=0.28), or the combined samples (P=0.72). There was also no significant association observed between CNTF genotype and BMI in the BLSA (P=0.59), the STORM (P=0.34) or the combined (P=0.56) samples. In addition, we were unable to detect a significant association between CNTF genotype and total body fat (P=0.95) or fat-free mass (P=0.86) in the BLSA cohort. Our results do not support an effect of the CNTF null allele on body composition, contrary to previous findings.

Adult↗
PubMed2004

Vitamin D receptor genotype is associated with fat-free mass and sarcopenia in elderly men.

We investigated the association of vitamin D receptor (VDR) genotype with fat-free mass (FFM) in a cohort of 302 older (aged 58-93 years) Caucasian men who underwent body composition analysis by dual-energy X-ray absorptiometry, and completed questionnaires addressing comorbidities, physical activity, and dietary intake. All participants were genotyped for a VDR translation start site (FokI) polymorphism [FF (37.7%), Ff (48.4%), and ff (13.9%)] and the previously studied BsmI polymorphism [BB (24.9%), Bb (37.7%), and bb (37.4%)]. The BsmI polymorphism was not associated with FFM in any analysis; however, the FokI polymorphism was significantly associated with total FFM, appendicular FFM, and relative (kg/m(2)) appendicular FFM (all p <.05), with the FF group demonstrating significantly lower FFM than the Ff and ff groups (e.g., total FFM: FF = 57.6 +/- 0.4, Ff = 59.4 +/- 0.4, ff = 59.4 +/- 0.7 kg; p <.02). Age-adjusted logistic regression revealed a 2.17-fold higher risk for sarcopenia (defined previously as appendicular FFM <7.26 kg/m(2)) in FF homozygotes (95% CI [confidence interval] = 1.19-3.85; p =.03) compared to men with one or more f alleles. The VDR translation start site (FokI) polymorphism is significantly associated with FFM and sarcopenia in this cohort of older Caucasian men.

Aged↗
PubMed2004

Myostatin: a therapeutic target for skeletal muscle wasting.

PURPOSE OF REVIEW: This review discusses recent developments in myostatin research, focusing on the basic actions of myostatin on skeletal muscle, the identification of key regulatory elements of the myostatin pathway, and the promise of myostatin as a therapeutic target in muscle-related disorders. RECENT FINDINGS: In addition to a well-characterized role in muscle development, recent research advances have solidified the importance of myostatin in adult muscle, although questions remain. A number of possible regulatory proteins for myostatin have been identified, showing a complex picture of myostatin regulation that requires clarification. The identification of an antimyostatin monoclonal antibody (JA16) shows the promise of myostatin as a target for muscle-wasting disorders; the antibody has already been shown to increase muscle mass in healthy older mice and muscle function in postnatal mdx mice. SUMMARY: Since its discovery in 1997, myostatin has quickly been established as a key regulator of skeletal muscle mass. Recent developments strengthen the idea that myostatin will be an important therapeutic target for muscle-wasting-related disorders, and as more details of myostatin regulation and its mechanisms of action are clarified, myostatin will continue to dominate the skeletal muscle development and muscle-wasting literature.

Animals↗