Biomedical subjects

Robert E Ferrell

Publications and source records attributed to Robert E Ferrell.

At least 19 recordsLinked to original sources

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

C-reactive protein genotypes affect baseline, but not exercise training-induced changes, in C-reactive protein levels.

OBJECTIVE: The goal of this study is to determine whether C-reactive protein (CRP) gene variants affect baseline and training-induced changes in plasma CRP levels. METHODS AND RESULTS: Sixty-three sedentary men and women aged 50 to 75 years old underwent baseline testing (Vomax, body composition, CRP levels). They repeated these tests after 24 weeks of exercise training while on a low-fat diet. The CRP +219G/A variant significantly associated with CRP levels before and after training after accounting for the effects of demographic and biological variables. CRP -732A/G genotype was significantly related on a univariate basis to CRP levels after training. The CRP +29T/A variant did not affect CRP levels before or after training. In regression analyses, the +219 and -732 variants each had significant effects on CRP levels before and after training. Subjects homozygous for the common A/G -732/+219 haplotype exhibited the highest CRP levels, and having the rare allele at either site was associated with significantly lower CRP levels. CRP levels decreased significantly with training (-0.38+/-0.18 mg/L; P=0.03). However, none of the CRP variants was associated with the training-induced CRP changes. CONCLUSIONS: CRP +219G/A and -732A/G genotypes and haplotypes and exercise training appear to modulate CRP levels. However, training-induced CRP reductions appear to be independent of genotype at these loci.

Adenine↗

PubMed2004

Influence of the interleukin-6 -174 G/C gene polymorphism on exercise training-induced changes in glucose tolerance indexes.

A polymorphism in the IL-6 gene, a G-to-C substitution 176 bp upstream of the ATG translation initiation site, has been associated with diabetes prevalence and insulin resistance. Interventions including exercise training are frequently used to modify cardiovascular disease risk factors. Consequently, this project examined associations between the IL-6 -174 genotype and oral glucose tolerance test outcomes in 50- to 75-yr-old sedentary men and postmenopausal women before and after aerobic exercise training. Among the 87 individuals who started the study, 56 were retested after 6 mo of aerobic exercise training. Subject characteristics at baseline did not differ between the IL-6 genotype groups with the exception of fasting glucose, which was higher (P = 0.02, covariates age, gender, and ethnicity) in the CC genotype group. The training-induced change in glucose area under the curve during the oral glucose tolerance test varied between the IL-6 -174 genotype groups (P = 0.05, covariates age, gender, ethnicity, baseline glucose area under the curve, and percent body fat change) with a significant decrease occurring only in the GG genotype group. Insulin outcomes did not differ among the groups at baseline or after training. Training-induced changes in weight, percent body fat, maximal oxygen consumption, fasting glucose, and an insulin sensitivity index also changed similarly among the genotype groups. In conclusion, fasting glucose and the extent to which glucose tolerance changes with exercise training may be influenced by the IL-6 -174 gene polymorphism.

Age Factors↗

PubMed2004

Age-related maculopathy: a genomewide scan with continued evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions.

Age-related maculopathy (ARM), or age-related macular degeneration, is one of the most common causes of visual impairment in the elderly population of developed nations. In a combined analysis of two previous genomewide scans that included 391 families, containing up to 452 affected sib pairs, we found linkage evidence in four regions: 1q31, 9p13, 10q26, and 17q25. We now have added a third set of families and have performed an integrated analysis incorporating 530 families and up to 736 affected sib pairs. Under three diagnostic models, we have conducted linkage analyses using parametric (heterogeneity LOD [HLOD] scores under an autosomal dominant model) and nonparametric (Sall statistic) methods. There is ongoing evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions. If we treat the third set of families as a replication set, then two regions (10q26 and 17q25) are replicated, with LOD scores >1.0. If we pool all our data together, then four regions (1q31, 2q14.3, 10q26, and 17q25) show HLOD or Sall scores > or =2.0. Within the 1q31 region, we observed an HLOD of 2.72 (genomewide P=.061) under our least stringent diagnostic model, whereas the 17q25 region contained a maximal HLOD of 3.53 (genomewide P=.007) under our intermediate diagnostic model. We have evaluated our results with respect to the findings from several new independent genomewide linkage studies and also have completed ordered subset analyses (OSAs) with apolipoprotein E alleles, smoking history, and age at onset as stratifying covariates. The OSAs generate the interesting hypothesis that the effect of smoking on the risk of ARM is accentuated by a gene in the 10q26 region--a region implicated by four other studies.

Chromosomes, Human, Pair 1↗

PubMed2004

Steroid sulfatase gene variation and DHEA responsiveness to resistance exercise in MERET.

Genetic influences and endurance exercise have been shown to alter circulating concentrations of dehydroepiandrosterone (DHEA) and its sulfated conjugate, DHEAS. We hypothesized that acute resistance exercise (RE) and training (RET) would increase DHEA steroids, and the magnitude of the increase would be influenced by a steroid sulfatase (STS) gene variation. Fasting blood samples were collected before and after the first (S1) and last (S30) session of a 10-wk RET program in 62 men and 58 women [age: 21.0 yr (2.4)]. Acute RE increased both DHEA [+2.8 (0.4), S1; +1.6 ng/ml (0.4), S30; P < 0.001] and DHEAS [+154 (24), S1; +166 ng/ml (15), S30; P < 0.001] and decreased DHEAS:DHEA [-27 (8), S1; -15 (7), S30; P < 0.01]. RET reduced resting DHEAS (-122 ng/ml, P < 0.01) and decreased DHEA response to RE (-50%, P < 0.05). Subjects with an STS "G" allele (n = 36) had greater acute changes in DHEA [+4.4 (0.7) vs. +2.0 ng/ml (0.5), S1; +3.2 (0.6) vs. +1.0 ng/ml (0.4), S30; P < 0.01] and DHEAS:DHEA [-37 (11) vs. 5 (7), S30, P < 0.05] than those subjects with only an "A" allele (n = 84). The observed increase in DHEA and DHEAS and decrease in DHEAS:DHEA suggest RE-induced STS activation which is influenced by the STS polymorphism.

Adult↗

PubMed2004

Haplotypes of the monoamine oxidase genes and the risk for substance use disorders.

Monoamine oxidase A (MAOA) locus is an attractive candidate for exploring genetic contribution to the variation in the risk for substance use disorders (SUD) because of its important role in the metabolism of neurotransmitters, including dopamine and serotonin. Prior findings have suggested an association of the MAOA gene with the risk for early onset SUD. To extend this research, we genotyped four MAOA markers (two VNTR polymorphisms and two SNPs) and built a cladogram reflecting the evolutionary history of MAOA haplotypes [Nguyen et al., under review]. The cladogram served as the framework for nested ANOVA and logit analyses of association between MAOA and indices of liability to SUD (diagnosis, age of onset, and a dimensional index of substance use related problems) in a sample of adult males of European ancestry. Whereas no association was found for the categorical diagnosis, a significant relationship was detected between the dimensional liability indices and MAOA haplotypes. Overall, our results, albeit not definitive, are consistent with the hypothesis that variants in MAOA account for a small portion of the variance of SUD risk, possibly mediated by liability to early onset behavioral problems.

Adult↗

PubMed2004

Prospective analysis of mannose-binding lectin genotypes and coronary artery disease in American Indians: the Strong Heart Study.

BACKGROUND: Mannose-binding lectin (MBL) is a circulating immune factor responsible for opsonization of pathogens and directly activating complement. Common variations in the MBL gene are responsible for an opsonic deficiency that affects 5% to 7% of whites and are associated with increased susceptibility to infections. After a preliminary report associating these variations with coronary artery disease (CAD), we determined MBL genotypes in 3 American Indian communities experiencing an increased mortality and morbidity from CAD. METHODS AND RESULTS: We examined DNA from 434 participants in a population-based cohort, the Strong Heart Study. Genotypes for 3 common MBL coding variations and 1 promoter polymorphism were determined. The frequency of a composite genotype that conferred low MBL levels was 20.7% in 217 cases and 11.1% in matched controls without CAD. A conditional logistic regression model indicated a univariate OR for CAD of 2.3 (95% CI 1.3 to 4.2, P=0.005) for the variant genotypes. After adjustment for demographic and CAD risk factors, including type 2 diabetes mellitus, fibrinogen, triglycerides, and hypertension, the OR was 3.2 (95% CI 1.5 to 7.0, P=0.004). CONCLUSIONS: Variant MBL genotypes coding for markedly diminished levels of MBL are predictive of CAD. After adjustment for multiple traditional risk factors for ischemic heart disease, this association remains significant. A high prevalence of variant MBL alleles and CAD in this population suggests that potentially important public health benefits may accrue from future interventions based on these genotypes.

Cohort Studies↗

PubMed2004

The genetic component of middle ear disease in the first 5 years of life.

OBJECTIVE: To determine the genetic component of time with middle ear effusion (MEE) and episodes of MEE and acute otitis media. DESIGN: Prospective twin/triplet cohort. SETTING: Research center at a tertiary pediatric hospital. PARTICIPANTS: A total of 168 healthy same-sex twin and 7 same-sex triplet sets were recruited by age 2 months. INTERVENTIONS: Longitudinal assessment of middle ear status by pneumatic otoscopy and tympanometry at monthly evaluations, and at examinations during upper respiratory tract infections or symptoms of middle ear disease. OUTCOME MEASURES: Proportion of time with MEE and episodes of acute otitis media and MEE. RESULTS: Of the 140 sets for which zygosity was obtained, 114 were followed up to age 3 years and 83 sets to age 5 years. The heritability estimate for proportion of time with MEE in the first 5 years of life was 0.72 (P<.001). The correlation of proportion of time with MEE between children within a set was significantly higher in monozygotic sets (0.65-0.77) than in dizygotic sets (0.31-0.39) for each year to age 3 years. In the fourth and fifth years of life, the correlations decreased in both monozygotic and dizygotic twin sets. CONCLUSIONS: Findings for the first 2 years of follow-up have been previously published and indicate a strong genetic component to the proportion of time with MEE. In the present report, which details the entire 5-year follow-up, the effect of this component appears to attenuate after the third year but its cumulative effect remains significant after 5 years.

Acoustic Impedance Tests↗

PubMed2004

Genetic variation in fatty acid-binding protein-4 and peroxisome proliferator-activated receptor gamma interactively influence insulin sensitivity and body composition in males.

Obesity and type 2 diabetes are closely related, multifactorial metabolic conditions characterized by alterations in energy metabolism and glucose homeostasis, respectively. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-dependent transcription factor that regulates genes involved in lipid and glucose homeostasis, including the adipocyte-specific fatty acid-binding protein (FABP4). In turn, FABP4 binds fatty acids and transports them to the nucleus where the FABP4/fatty acid complex activates PPARgamma in a positive feedback loop. In this study, we tested the hypothesis that the polymorphisms, FABP4-376 and PPARgamma Pro12Ala, interactively influence insulin sensitivity and body composition in nondiabetic, Hispanic and non-Hispanic white males (n = 314) participating in the San Luis Valley Diabetes Study (SLVDS). Although the individual sites were not statistically significantly associated with any of the outcomes, we found statistically significant interaction terms in 2-way analysis of covariance (ANCOVA) models for homeostasis model assessment of insulin resistance (HOMA-IR) (P =.014) and lean mass (P =.019). While the PPARgamma Pro12Ala site was the only statistically significant predictor of fat mass in the 2-way model (P =.012), the FABP4 and PPARgamma main effect terms individually became stronger when considered in one model compared with the analysis of each polymorphism separately. These findings provide evidence that FABP4 and PPARgamma work together to influence a biologic pathway affecting insulin sensitivity and body composition, illustrating the importance of investigating the joint effect of genes in determining susceptibility for complex disease.

Adult↗

PubMed2004

Genetic variation in uncoupling protein 3 is associated with dietary intake and body composition in females.

The uncoupling proteins (UCPs) are a family of mitochondrial transport proteins that promote proton leakage across the inner mitochondrial membrane, uncoupling oxidative phosphorylation from adenosine triphosphate (ATP) production and releasing energy as heat. Variation in these genes may disrupt biochemical pathways influencing thermogenesis, energy metabolism, and fuel substrate partitioning and oxidation, which may in turn predispose to obesity. We genotyped polymorphisms in UCP2 and UCP3 in a sample of nondiabetic participants (n = 722) of the San Luis Valley Diabetes Study (SLVDS) and found female-specific associations between UCP3 polymorphisms and measures of dietary intake and body composition. The UCP3-5 variant was statistically significantly associated with total caloric intake (P =.012), fat intake (P =.011), fat mass (P =.004), and lean mass (P =.013), with the C allele corresponding to higher dietary intake and lower fat mass and lean mass. The UCP3p-55 and the UCP3-3 polymorphisms, which were in high linkage disequilibrium (D' = 0.9776), showed similar patterns of association with total caloric intake (P =.031 and P =.042, respectively) and lean mass (P =.035 and P =.059, respectively), with the rare alleles corresponding to higher total intake and lean mass. No statistically significant associations were detected between the outcome variables and polymorphisms in UCP2. Two-way analysis of covariance (ANCOVA), used to evaluate the multi-locus effects and interactions between UCP3-5 and UCP3p-55, showed association with the main effect terms, but no evidence for statistically significant interaction between UCP3-5 and UCP3p-55 in regard to dietary intake. The UCP3-5 polymorphism was the only statistically significant genetic predictor of fat mass. The lean mass model showed no statistically significant association with either UCP3 variant. These results support a role for UCP3 in fuel substrate management and energy metabolism, which may influence body weight regulation.

Alleles↗

PubMed2004

Socio-economic status covaries with central nervous system serotonergic responsivity as a function of allelic variation in the serotonin transporter gene-linked polymorphic region.

It was reported recently that exposure to an adverse rearing environment lowers central nervous system (CNS) serotonergic activity in a nonhuman primate (rhesus monkeys), but only among animals having the shorter variant of a functional, biallelic repeat polymorphism in the regulatory region of the serotonin transporter (5-HTT) gene. Because repeat variants of the same core sequence affect transcriptional efficiency of the 5-HTT gene in humans, we examined whether biallelic variation in the 5-HTT gene-linked polymorphic region (5-HTTLPR) acts analogously to modulate a previously described association between socio-economic status (SES) and CNS serotonergic function. The 5-HTTLPR was genotyped in 139 adult men and women (n = 75 and 64) who were administered a standard neuroendocrine challenge to assess central serotonergic responsivity (plasma prolactin (PRL) response to the serotonin releasing agent, fenfluramine). Socio-economic status was estimated from reported income and years of education. Hierarchical linear regression showed serotonergic responsivity to be predicted by the interaction of 5-HTTLPR genotype and SES (p = 0.018). Individuals of lower income and less education had lower peak PRL concentrations following administration of fenfluramine than did subjects ranking higher on these dimensions, but only among persons possessing at least one 5-HTTLPR short allele. Within genotype, SES covaried moderately with the PRL response to fenfluramine among subjects who were homozygous for the short allele (r18 = 0.50, p < 0.03). A similar association was present at lesser magnitude in heterozygotes (r70 = 0.24, p < 0.05) and absent among subjects homozygous for the long allele (r45 = -0.04, n.s.). Findings were comparable for men and women and persisted on re-analysis restricted to persons without current Axis I psychopathology. We conclude that allelic variation at 5-HTTLPR moderates the influence of social position on CNS serotonergic responsivity.

Adult↗

PubMed2004

Association between body fat response to exercise training and multilocus ADR genotypes.

OBJECTIVE: To examine the contribution of adrenergic receptor (ADR) gene polymorphisms and their gene-gene interactions to the variability of exercise training-induced body fat response. RESEARCH METHODS AND PROCEDURES: This was an intervention study that used a volunteer sample of 70 healthy, sedentary men (n = 29) and postmenopausal women (n = 41) 50 to 75 years of age, with a BMI < or = 37 kg/m2, from the Washington, DC, metropolitan area. Participants completed 6 weeks of dietary stabilization (American Heart Association diet) before 24 weeks of supervised aerobic exercise training. Diet was maintained throughout the intervention. Change in percent total body fat, percent trunk fat, and fat mass by DXA in ADR genotype groups (Glu12/Glu9 alpha2b-ADR, Trp64Arg beta3-ADR, and Gln27Glu beta2-ADR) at baseline and after 24 weeks of aerobic exercise training was measured. RESULTS: In multivariate analysis (covariates: age, gender, and baseline value of phenotype), best fit models for percent total body and trunk fat response to exercise training retained main effects of all three ADR gene loci and the effects of each gene-gene interaction (p = 0.009 and 0.003, respectively). Similarly, there was a trend for the fat mass response model (p = 0.03). The combined genetic factors explained 17.5% of the overall model variability for percent total body fat, 22% for percent trunk fat, and 10% for fat mass. DISCUSSION: The body fat response to exercise training in older adults is associated with the combined effects of the Glu12/Glu9 alpha2b-, Trp64Arg beta3-, and Gln27Glu beta2-ADR gene variants and their gene-gene interactions.

Adipose Tissue↗

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

Beta2- and beta3-adrenergic receptor polymorphisms and exercise hemodynamics in postmenopausal women.

We sought to determine whether common genetic variations at the beta2 (beta2-AR, Gln27Glu) and beta3 (beta3-AR, Trp64Arg) adrenergic receptor gene loci were associated with cardiovascular (CV) hemodynamics during maximal and submaximal exercise. CV hemodynamics were assessed in 62 healthy postmenopausal women (20 sedentary, 22 physically active, and 20 endurance athletes) during treadmill exercise at 40, 60, 80, and 100% maximal O2 uptake using acetylene rebreathing to quantify cardiac output. The beta2-AR genotype and habitual physical activity (PA) levels interacted to significantly associate with arteriovenous O2 difference (a-vDO2) during submaximal exercise (P = 0.05), with the highest submaximal exercise a-vDO2 in sedentary women homozygous for the beta2-AR Gln allele and no genotype-dependent differences in submaximal exercise a-vDO2 in physically active and athletic women. The beta2-AR genotype also was independently associated with a-vDO2 during submaximal (P = 0.004) and approximately 100% maximal O2 uptake exercise (P = 0.006), with a 1.2-2 ml/100 ml greater a-vDO2 in the Gln/Gln than in the Glu/Glu genotype women. The beta3-AR genotype, independently or interacting with habitual PA levels, was not significantly associated with any CV hemodynamic variables during submaximal or maximal exercise. Thus it appears that the beta2-AR genotype, both independently and interacting with habitual PA levels, is significantly associated with a-vDO2 during exercise in postmenopausal women, whereas the beta3-AR genotype does not appear to be associated with any maximal or submaximal exercise CV hemodynamic responses in postmenopausal women.

Aged↗

PubMed2004

Selected genetic polymorphisms and plasma coagulation factor VII changes with exercise training.

We assessed the effects of coagulation factor VII (FVII) gene polymorphisms, lipid-related polymorphisms, and exercise training-induced plasma lipoprotein lipid changes on FVII level changes with exercise training in middle- to older-aged men and women. Forty-six healthy sedentary men and women were stabilized on a low-fat diet and then underwent baseline testing, 6 mo of endurance exercise training, and final testing. Plasma FVII-Ag levels decreased with exercise training (106.7 +/- 1.4 vs. 104.2 +/- 1.6%, P = 0.005). There were no significant differences in FVII-Ag changes with exercise training between -323 (0/10 bp)/-401 (G/T) haplotype or -402 (G/A) genotype groups. FVII-Ag changes with training were not correlated with changes in plasma lipoprotein lipids. In linear regression analyses, FVII-Ag changes with training remained significant after adjusting for training-induced plasma lipoprotein lipid changes (P = 0.01). FVII changes with training were associated with apolipoprotein E genotype (P = 0.012); this relationship was still evident after adjusting for training-induced plasma lipoprotein lipid changes (P = 0.047). FVII changes with training also were significantly associated with human ATPase binding cassette-1 genotype (P = 0.018); this relationship persisted after accounting for the effect of the training-induced plasma lipoprotein lipid changes (P = 0.045). We conclude that plasma FVII-Ag changes with exercise training are more closely related to selected lipid-related genotypes than FVII gene promoter variants.

Aged↗

PubMed2003

Androgen receptor CAG repeat polymorphism is associated with cognitive function in older men.

BACKGROUND: Androgen receptors are located throughout the brain, especially in regions involved with learning and memory. Different lengths of a CAG (glutamine) repeat polymorphism in exon 1 of the androgen receptor gene may influence androgen action, with longer repeat lengths conferring decreased androgen sensitivity. METHODS: We sought to determine if this CAG polymorphism was associated with cognition in older men. RESULTS: Among 301 community-dwelling white men (mean age, 73.0 +/- 7.1), greater CAG repeat length was associated with lower scores on three cognitive tests (p <.05 for all). In addition, 12 participants (9.8%) had cognitive impairment in the low tertile of CAG repeat length whereas 29 (16.3%) had cognitive impairment in the two higher tertiles (odds ratio = 1.8; 95% confidence interval =.9-3.7). CONCLUSIONS: Research should be directed at identifying the mechanism for this association and to determine if treatment with testosterone prevents cognitive decline.

Aged↗