Tags

Type your tag names separated by a space and hit enter

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.

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.

Links

  • PMC Free PDF
  • PMC Free Full Text
  • FREE Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.

    , , , ,

    Source

    Environmental health perspectives 111:3 2003 Mar pg 335-41

    MeSH

    Adult
    Aged
    Aged, 80 and over
    Aging
    Bone and Bones
    Creatinine
    Cross-Sectional Studies
    Environmental Exposure
    Exons
    Genotype
    Humans
    Kidney
    Kidney Diseases
    Lead
    Male
    Middle Aged
    Polymorphism, Genetic
    Porphobilinogen Synthase
    Regression Analysis
    Uric Acid
    Veterans

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    12611663

    Citation

    Wu, Ming-Tsang, et al. "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, vol. 111, no. 3, 2003, pp. 335-41.
    Wu MT, Kelsey K, Schwartz J, et al. 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. Environ Health Perspect. 2003;111(3):335-41.
    Wu, M. T., Kelsey, K., Schwartz, J., Sparrow, D., Weiss, S., & Hu, H. (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), pp. 335-41.
    Wu MT, et al. 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. Environ Health Perspect. 2003;111(3):335-41. PubMed PMID: 12611663.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - 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. AU - Wu,Ming-Tsang, AU - Kelsey,Karl, AU - Schwartz,Joel, AU - Sparrow,David, AU - Weiss,Scott, AU - Hu,Howard, PY - 2003/3/4/pubmed PY - 2003/6/7/medline PY - 2003/3/4/entrez SP - 335 EP - 41 JF - Environmental health perspectives JO - Environ. Health Perspect. VL - 111 IS - 3 N2 - 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. SN - 0091-6765 UR - https://www.unboundmedicine.com/medline/citation/12611663/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_ L2 - https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.5504?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -