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.

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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.

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dc.contributor.author Kelsey, Karl
dc.contributor.author Hu, Howard
dc.contributor.author Wu, Ming-Tsang
dc.contributor.author Schwartz, Joel David
dc.contributor.author Sparrow, David
dc.contributor.author Weiss, Scott Tillman
dc.date.accessioned 2011-05-10T02:04:32Z
dc.date.issued 2003
dc.identifier.citation Wu, Ming-Tsang, Karl Kelsey, Joel Schwartz, David Sparrow, Scott Weiss, and Howard Hu. 2003. 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. Environmental Health Perspectives 111(3): 335-341. en_US
dc.identifier.issn 0091-6765 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4885976
dc.description.abstract 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. en_US
dc.language.iso en_US en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241391/pdf/ en_US
dash.license LAA
dc.subject δ- aminolevulinic acid dehydratase en_US
dc.subject bone lead en_US
dc.subject serum creatinine en_US
dc.subject serum uric acid en_US
dc.title 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. en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Environmental Health Perspectives en_US
dash.depositing.author Weiss, Scott Tillman
dc.date.available 2011-05-10T02:04:32Z
dash.affiliation.other SPH^Environmental+Occupational Medicine+Epi en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other SPH^Exposure Epidemiology and Risk Program en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other SPH^Molecular+Integrative Physiological Sci Prog en_US

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