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Delta-aminolevulinic acid dehydratase polymorphism and the relation between low level lead exposure and the Mini-Mental Status Examination in older men: the Normative Aging Study.

Abstract

OBJECTIVE

To determine whether a polymorphism the in delta-aminolevulinic acid dehydratase (ALAD) gene modifies the neurotoxicity of lead in older adults.

METHODS

The authors studied men participating in the Department of Veterans Affairs' Normative Aging Study, assessing their recent exposure to lead by measuring blood lead (n = 915) at each triennial clinic visit, and, beginning in 1991, assessing their cumulative exposure by measuring lead levels in tibia (n = 722) and patella (n = 720), using K-shell x ray fluorescence. Starting in 1993 and again at each triennial visit, the authors administered the Mini-Mental State Examination (MMSE) to assess their cognitive functioning. The relation of the lead biomarkers to MMSE score was evaluated and this association was compared among men who carried the variant allele, ALAD-2, versus men without the allele.

RESULTS

Sixteen per cent of men carried the ALAD-2 allele. Median tibia and patella lead levels (first-third quartile) were 19 (13-28) and 27 (18-39) microg/g. Blood lead levels were consistent with non-occupational exposure: only 6% of men had levels > or =10 microg/dl. In multivariable adjusted analyses, higher levels of blood lead were associated with poorer performance on the MMSE. This association was most pronounced among ALAD-2 carriers, among whom a 3 microg/dl increment in blood lead (the interquartile range) was associated with a 0.26 point lower mean MMSE score (95% CI -0.54 to 0.01), compared with a 0.04 point lower score (95% CI -0.16 to 0.07) among non-carriers. The modest 0.22 point difference in these associations did not attain statistical significance, however (p(interaction) = 0.13). The associations between bone lead levels and MMSE score did not vary by ALAD-2 status.

CONCLUSIONS

Although not statistically significant, these findings suggest that ALAD genotype may modify blood lead's adverse association with cognition among older men who had community exposures to lead. However, despite a relatively large sample size and the use of sensitive methods for measuring lead burden, the evidence overall was fairly weak.

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  • Authors+Show Affiliations

    ,

    Department of Environmental Health, Harvard School of Public Health, Landmark Center, Boston, MA 02215, USA. jweuve@hsph.harvard.edu

    , , , , , , , ,

    Source

    MeSH

    Adult
    Aged
    Aged, 80 and over
    Cognition
    Cohort Studies
    Environmental Exposure
    Genetic Predisposition to Disease
    Genotype
    Humans
    Lead
    Lead Poisoning, Nervous System, Adult
    Longitudinal Studies
    Male
    Mental Status Schedule
    Middle Aged
    Patella
    Polymorphism, Genetic
    Porphobilinogen Synthase
    Tibia

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    16757504

    Citation

    Weuve, J, et al. "Delta-aminolevulinic Acid Dehydratase Polymorphism and the Relation Between Low Level Lead Exposure and the Mini-Mental Status Examination in Older Men: the Normative Aging Study." Occupational and Environmental Medicine, vol. 63, no. 11, 2006, pp. 746-53.
    Weuve J, Kelsey KT, Schwartz J, et al. Delta-aminolevulinic acid dehydratase polymorphism and the relation between low level lead exposure and the Mini-Mental Status Examination in older men: the Normative Aging Study. Occup Environ Med. 2006;63(11):746-53.
    Weuve, J., Kelsey, K. T., Schwartz, J., Bellinger, D., Wright, R. O., Rajan, P., ... Hu, H. (2006). Delta-aminolevulinic acid dehydratase polymorphism and the relation between low level lead exposure and the Mini-Mental Status Examination in older men: the Normative Aging Study. Occupational and Environmental Medicine, 63(11), pp. 746-53.
    Weuve J, et al. Delta-aminolevulinic Acid Dehydratase Polymorphism and the Relation Between Low Level Lead Exposure and the Mini-Mental Status Examination in Older Men: the Normative Aging Study. Occup Environ Med. 2006;63(11):746-53. PubMed PMID: 16757504.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Delta-aminolevulinic acid dehydratase polymorphism and the relation between low level lead exposure and the Mini-Mental Status Examination in older men: the Normative Aging Study. AU - Weuve,J, AU - Kelsey,K T, AU - Schwartz,J, AU - Bellinger,D, AU - Wright,R O, AU - Rajan,P, AU - Spiro,A,3rd AU - Sparrow,D, AU - Aro,A, AU - Hu,H, Y1 - 2006/06/06/ PY - 2006/6/8/pubmed PY - 2006/11/15/medline PY - 2006/6/8/entrez SP - 746 EP - 53 JF - Occupational and environmental medicine JO - Occup Environ Med VL - 63 IS - 11 N2 - OBJECTIVE: To determine whether a polymorphism the in delta-aminolevulinic acid dehydratase (ALAD) gene modifies the neurotoxicity of lead in older adults. METHODS: The authors studied men participating in the Department of Veterans Affairs' Normative Aging Study, assessing their recent exposure to lead by measuring blood lead (n = 915) at each triennial clinic visit, and, beginning in 1991, assessing their cumulative exposure by measuring lead levels in tibia (n = 722) and patella (n = 720), using K-shell x ray fluorescence. Starting in 1993 and again at each triennial visit, the authors administered the Mini-Mental State Examination (MMSE) to assess their cognitive functioning. The relation of the lead biomarkers to MMSE score was evaluated and this association was compared among men who carried the variant allele, ALAD-2, versus men without the allele. RESULTS: Sixteen per cent of men carried the ALAD-2 allele. Median tibia and patella lead levels (first-third quartile) were 19 (13-28) and 27 (18-39) microg/g. Blood lead levels were consistent with non-occupational exposure: only 6% of men had levels > or =10 microg/dl. In multivariable adjusted analyses, higher levels of blood lead were associated with poorer performance on the MMSE. This association was most pronounced among ALAD-2 carriers, among whom a 3 microg/dl increment in blood lead (the interquartile range) was associated with a 0.26 point lower mean MMSE score (95% CI -0.54 to 0.01), compared with a 0.04 point lower score (95% CI -0.16 to 0.07) among non-carriers. The modest 0.22 point difference in these associations did not attain statistical significance, however (p(interaction) = 0.13). The associations between bone lead levels and MMSE score did not vary by ALAD-2 status. CONCLUSIONS: Although not statistically significant, these findings suggest that ALAD genotype may modify blood lead's adverse association with cognition among older men who had community exposures to lead. However, despite a relatively large sample size and the use of sensitive methods for measuring lead burden, the evidence overall was fairly weak. SN - 1470-7926 UR - https://www.unboundmedicine.com/medline/citation/16757504/Delta_aminolevulinic_acid_dehydratase_polymorphism_and_the_relation_between_low_level_lead_exposure_and_the_Mini_Mental_Status_Examination_in_older_men:_the_Normative_Aging_Study_ L2 - http://oem.bmj.com/cgi/pmidlookup?view=long&pmid=16757504 DB - PRIME DP - Unbound Medicine ER -