Biomedical subjects

David Sparrow

Publications and source records attributed to David Sparrow.

27 records · Page 2Linked to original sources

PubMed2004

Association between hemochromatosis genotype and lead exposure among elderly men: the normative aging study.

Because body iron burden is inversely associated with lead absorption, genes associated with hemochromatosis may modify body lead burden. Our objective was to determine whether the C282Y and/or H63D hemochromatosis gene (HFE) is associated with body lead burden. Patella and tibia lead levels were measured by K X-ray fluorescence in subjects from the Normative Aging Study. DNA samples were genotyped for C282Y and H63D using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). A series of multivariate linear regression models were constructed with bone or blood lead as dependent variables; age, smoking, and education as independent variables; and C282Y or H63D as independent risk factors and/or effect modifiers. Of 730 subjects, 94 (13%) carried the C282Y variant and 183 (25%) carried the H63D variant. In the crude analysis, mean tibia, patella, and blood lead levels were consistently lower in carriers of either HFE variant compared with levels in subjects with wild-type genotypes. In multivariate analyses that adjusted for age, smoking, and education, having an HFE variant allele was an independent predictor of significantly lower patella lead levels (p < 0.05). These data suggest that HFE variants have altered kinetics of lead accumulation after exposure. Among elderly men, subjects with HFE variants had lower patella lead levels. These effects may be mediated by alterations in lead toxicokinetics via iron metabolic pathways regulated by the HFE gene product and body iron stores.

Aged↗

PubMed2004

Determinants of bone and blood lead levels among minorities living in the Boston area.

We measured blood and bone lead levels among minority individuals who live in some of Boston's neighborhoods with high minority representation. Compared with samples of predominantly white subjects we had studied before, the 84 volunteers in this study (33:67 male:female ratio; 31-72 years of age) had similar educational, occupational, and smoking profiles and mean blood, tibia, and patella lead levels (3 microg/dL, 11.9 microg/g, and 14.2 microg/g, respectively) that were also similar. The slopes of the univariate regressions of blood, tibia, and patella lead versus age were 0.10 microg/dL/year (p < 0.001), 0.45 microg/g/year (p < 0.001), and 0.73 microg/g/year (p < 0.001), respectively. Analyses of smoothing curves and regression lines for tibia and patella lead suggested an inflection point at 55 years of age, with slopes for subjects greater than or equal to 55 years of age that were not only steeper than those of younger subjects but also substantially steeper than those observed for individuals > 55 years of age in studies of predominantly white participants. This apparent racial disparity at older ages may be related to differences in historic occupational and/or environmental exposures, or possibly the lower rates of bone turnover that are known to occur in postmenopausal black women. The higher levels of lead accumulation seen in this age group are of concern because such levels have been shown in other studies to predict elevated risks of chronic disease such as hypertension and cognitive dysfunction. Additional research on bone lead levels in minorities and their socioeconomic and racial determinants is needed.

Adult↗

PubMed2004

Lead, diabetes, hypertension, and renal function: the normative aging study.

In this prospective study, we examined changes in renal function during 6 years of follow-up in relation to baseline lead levels, diabetes, and hypertension among 448 middle-age and elderly men, a subsample of the Normative Aging Study. Lead levels were generally low at baseline, with mean blood lead, patella lead, and tibia lead values of 6.5 microg/dL, 32.4 microg/g, and 21.5 microg/g, respectively. Six percent and 26% of subjects had diabetes and hypertension at baseline, respectively. In multivariate-adjusted regression analyses, longitudinal increases in serum creatinine (SCr) were associated with higher baseline lead levels but these associations were not statistically significant. However, we observed significant interactions of blood lead and tibia lead with diabetes in predicting annual change in SCr. For example, increasing the tibia lead level from the midpoints of the lowest to the highest quartiles (9-34 microg/g) was associated with an increase in the rate of rise in SCr that was 17.6-fold greater in diabetics than in nondiabetics (1.08 mg/dL/10 years vs. 0.062 mg/dL/10 years; p < 0.01). We also observed significant interactions of blood lead and tibia lead with diabetes in relation to baseline SCr levels (tibia lead only) and follow-up SCr levels. A significant interaction of tibia lead with hypertensive status in predicting annual change in SCr was also observed. We conclude that longitudinal decline of renal function among middle-age and elderly individuals appears to depend on both long-term lead stores and circulating lead, with an effect that is most pronounced among diabetics and hypertensives, subjects who likely represent particularly susceptible groups.

Adult↗

PubMed2004

Beta 2-adrenergic receptor polymorphisms and haplotypes are associated with airways hyperresponsiveness among nonsmoking men.

STUDY OBJECTIVE: To investigate the relationship of common single nucleotide polymorphisms (SNPs) of the beta(2)-adrenergic receptor (AR) gene at codons 16 and 27, and the intermediate phenotype of airways hyperresponsiveness. DESIGN: A case-control study in 543 white men (152 case patients and 391 control subjects), who were nested in an ongoing longitudinal cohort. SETTING: Subjects were selected from the Normative Aging Study, an ongoing longitudinal cohort of healthy aging. PARTICIPANTS: Case patients were defined as those having a positive response to methacholine challenge testing. Control subjects were selected among those who did not have a diagnosis of asthma and who had no response to methacholine. RESULTS: There was a trend for an association of the Arg16 SNP genotype with airways hyperresponsiveness (odds ratio, 1.25; 95% confidence interval, 0.96 to 1.64 [in an additive model]). In stratified analyses, the effect of the Arg16 variant was seen mainly among nonsmokers. Smokers had increased risks for airway hyperresponsiveness regardless of genotype at either SNP. Using a program to estimate haplotype frequencies, three common haplotypes were identified. Adjusting for age, baseline FEV(1), serum IgE level, and smoking status, the Gly16/Gln27 haplotype was negatively associated with airways hyperresponsiveness in the full complement of case patients and control subjects (score statistic, - 2.43; p = 0.02). The effect of the beta(2)-AR haplotypes was much stronger among lifelong nonsmokers, among whom the Gly16/Gln27 haplotype remained negatively associated with airways hyperresponsiveness (score statistic, - 3.114; p = 0.002), whereas the Arg16/Gln27 haplotype was positively associated with airways hyperresponsiveness (score statistic, 3.142; p = 0.002). No effects were seen among ever-smokers. CONCLUSIONS: In this cohort of middle-aged to older white men, beta(2)-AR polymorphisms were associated with airways hyperresponsiveness, particularly among lifelong nonsmokers. Our results illustrate an instance in which greater power is obtained by performing haplotype analyses as opposed to single SNP analysis.

Adult↗

PubMed2003

Serum interferon-gamma is associated with longitudinal decline in lung function among asthmatic patients: the Normative Aging Study.

BACKGROUND: Cytokines are important mediators of the asthmatic response. A retrospective pilot study showed that serum levels of interleukin (IL)-5 and interferon (IFN)-gamma were related to lung function decline among asthmatic patients over the preceding 3 years. To confirm these findings, we tested the hypothesis that serum cytokines are associated with longitudinal lung function decline. METHODS: We conducted a prospective, longitudinal study of 25 asthmatic and 50 nonasthmatic men (median age, 63 years; range, 45 to 80 years) participating in the Normative Aging Study. All study subjects completed two consecutive triennial examinations, including spirometry, methacholine challenge testing, allergy skin testing, and phlebotomy. Serum levels were measured for IL-4, IL-5, IL-6, IL-8, IL-10, and IFN-gamma. RESULTS: Among asthmatic patients, a higher initial serum level of IFN-gamma was associated with a greater rate of decline of forced expiratory volume in 1 second (FEV1; beta = -67 mL/year per log increase in serum IFN-gamma, P = 0.04) and, to a lesser extent, of FEV1/forced vital capacity ratio (beta = -0.91%/year per log increase in serum IFN-gamma, P = 0.07) after adjusting for age, smoking status, and baseline level of lung function. Serum IL-5 level was associated with a rate of decline in FEV1 of borderline significance (beta = -61 mL/year per log increase in serum IL-5, P = 0.08) among asthmatic patients. These relationshipswere not observed among nonasthmatic patients. CONCLUSIONS: Serum levels of IFN-gamma are associated with subsequent rate of change in lung function among asthmatic patients in this cohort of middle-aged and older men, and may be useful as biologic markers of risk for accelerated lung function decline in population studies.

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PubMed2003

A delta-aminolevulinic acid dehydratase (ALAD) polymorphism may modify the relationship of low-level lead exposure to uricemia and renal function: the normative aging study.

In this study we investigated whether a known delta-aminolevulinic acid dehydratase (ALAD) exon 4 polymorphism has a modifying effect on the association of blood or bone lead level with uricemia and indices of renal function among middle-aged and elderly men. We performed a cross-sectional study of subjects who participated between 1991 and 1995 in the Department of Veterans Affairs Normative Aging Study. Information on blood lead levels, bone lead levels (measured by K-shell X-ray fluorescence), serum uric acid, serum creatinine, estimated creatinine clearance, and ALAD polymorphism status was available in 709 subjects. Regression models were constructed to examine the relationships of serum uric acid, serum creatinine, and estimated creatinine clearance to blood or bone lead level, stratified by genotype. We also adjusted for age, body mass index, blood pressure, smoking, alcohol consumption, and ingestion of analgesic medications (n = 638). Of the 709 subjects, 7 (1%) and 107 (15%) were homozygous and heterozygous for the variant (ALAD-2) allele, respectively. The mean (range) serum uric acid and creatinine levels were 6.5 (2.9-10.6) and 1.2 (0.6-2.5) mg/dL. No significant differences were found in serum uric acid, serum creatinine, or estimated creatinine clearance by ALAD genotype. However, after adjusting for other potential confounders, we found a significant linear relationship between serum uric acid and patella bone lead (p = 0.040) among the ALAD 1-2/2-2 genotype individuals above a threshold patellar lead level of 15 micro g/g. In contrast, among the wild-type (ALAD 1-1) individuals, there was a suggestion of a significant linear relationship of serum uric acid with patella bone lead (p = 0.141), but only after a threshold of 101 micro g/g. There was evidence of a significant (p = 0.025) interaction of tibia lead with genotype (ALAD 1-1 vs. ALAD 1-2/2-2) regarding serum creatinine as an outcome, but in the same linear regression model tibia lead alone was not a significant predictor of serum creatinine. Conversely, for estimated creatinine clearance, patella lead, but not the interaction of patella lead with genotype, was a significantly independent predictor (p = 0.026). Our findings suggest that ALAD genotype may modify the effect of lead on the renal excretion of uric acid as well as overall renal function among middle-aged and elderly men who had community (nonoccupational) exposures to lead. Additional research is needed to ascertain whether this constitutes a true gene-environment interaction and, if so, its clinical impact.

Adult↗

PubMed2002

Occupational determinants of bone and blood lead levels in middle aged and elderly men from the general community: the Normative Aging Study.

BACKGROUND: Few studies of the general population have investigated risk factors for elevated levels of lead in bone in relation to occupation. METHODS: Six hundred and fifty six community-exposed men had their bone and blood lead levels measured (by K-X-ray fluorescence). Based on their occupational histories, participants were categorized into those who worked in white-collar (WC) occupations (59%) or blue-collar (BC) occupations (41%). No subjects had worked in a primary lead industry (e.g., smelting). RESULTS: In multivariate regression models that adjusted for age, race, education, smoking, alcohol ingestion and retirement status, BC subjects had tibia and patella lead concentrations that were 5.5 (95% CI: 3.2-7.8) and 6.5 (95% CI: 3.1-9.8) microg/g higher than WC subjects, respectively. Interaction terms pairing race with occupational status indicated that in non-white BC subjects, tibia and patella lead levels were higher still by 11.3 (95% CI: -2 to 24.5) and 20.5 (95% CI: 1.2-39.8) microg/g, respectively. Blood lead levels were low for these mostly retired men (mean [SD]: 6.1 [3.9] microg/g) and in multivariate regression models, occupational status was not a significant predictor of blood lead levels; however, an interaction between race and occupational status was also suggested, with non-white BC subjects having blood lead levels that were predicted to be higher by 4.5 (95% CI: 0.3-8.7) microg/dl. CONCLUSIONS: Bone lead levels are higher in the men who worked in BC occupations even if they have not worked in primary lead-exposed occupations. This effect is markedly stronger in non-white BC workers and suggests an interaction between occupational exposures and race/ethnicity with respect to cumulative exposure to lead. A similar interaction was suggested by models of blood lead levels.

Adult↗

PubMed2002

Breathing easy: a prospective study of optimism and pulmonary function in the normative aging study.

Although there is good evidence that emotions are associated with chronic airways obstruction, evidence for the influence of psychological factors on the level and decline of pulmonary function is sparse. Optimism has been linked to enhanced well-being, whereas pessimism has been identified as a risk factor for poor physical health. This investigation examines prospectively the effects of optimism versus pessimism on pulmonary function. Data are from the Veterans Administration Normative Aging Study, an ongoing cohort of older men. In 1986, 670 men completed the revised Minnesota Multiphasic Personality Inventory from which we derived the bipolar Revised Optimism-Pessimism Scale. During an average of 8 years of follow-up, an average of 3 pulmonary function exams were obtained. Men with a more optimistic explanatory style had significantly higher levels of forced expiratory volume in 1 sec (FEV1) and forced vital capacity (both p < .01). Interactions between time and optimism suggested that rate of decline in FEV1 over time was slower in men with a more optimistic explanatory style relative to men who were more pessimistic. These data are the first to link optimism with higher levels of pulmonary function and slower rate of pulmonary function decline in older men, a protective effect that is independent of smoking.

Adult↗

PubMedDate not supplied

Season modifies the relationship between bone and blood lead levels: the Normative Aging Study.

Bone serves as a repository for 75% and 90-95% of lead in children and adults, respectively. Bone lead mobilization heightens during times of increased bone turnover, such as pregnancy, lactation, hyperthyroidism, and the rapid growth of childhood. Blood lead levels show seasonal periodicity. Children demonstrate peak blood lead levels in mid-summer and a secondary peak in late winter. Pregnant women demonstrate the highest mean blood lead levels in winter (January-March) and the lowest in summer (July-September). This fluctuation in blood lead levels may be related to seasonal patterns of environmental exposures, but it may also be partially related to the increased mobilization of bone lead stores during the winter months. We performed bone lead measurements using a K-x-ray fluorescent instrument to determine micrograms of lead per gram of bone mineral (parts per million) in middle-aged and elderly men who participated in the Normative Aging Study. We obtained measurements of blood and bone lead during the high sun exposure months of May-August (summer; n = 290); the intermediate sun exposure months of March, April, September, and October (spring/fall; n = 283); and the low sun exposure months of November-February (winter; n = 191). Mean blood lead concentrations were 5.8 microg/dl, 6.1 microg/dl, and 6.6 microg/dl for the summer, spring/fall, and winter, respectively. Mean patella (trabecular bone) lead concentrations were 34.3 microg/gm, 29.7 microg/gm, and 29.0 microg/gm for the summer, spring/fall, and winter time periods, respectively. In multivariate regression models, adjusted for age, smoking, alcohol ingestion, and dietary intake of iron and vitamin C, the authors found a strong interaction between season and bone lead level--with bone lead levels exerting an almost 2-fold greater influence on blood levels during the winter months than the summer months. The authors concluded that elevated blood lead levels in winter may be related to increased mobilization of endogenous bone lead stores, potentially from decreased exposure to sunlight, lower levels of activated vitamin D, and enhanced bone resorption.

Adult↗