TY - JOUR
T1 - Evidence of genetic effects on blood lead concentration
AU - Whitfield, John B.
AU - Dy, Veronica
AU - McQuilty, Robert
AU - Zhu, Gu
AU - Montgomery, Grant W.
AU - Ferreira, Manuel A.R.
AU - Duffy, David L.
AU - Neale, Michael C.
AU - Heijmans, Bas T.
AU - Heath, Andrew C.
AU - Martin, Nicholas G.
PY - 2007/8
Y1 - 2007/8
N2 - Background: Lead is an environmental pollutant that causes acute and chronic toxicity. Surveys have related mean blood lead concentrations to exogenous sources, including industrial activity, use of lead-based paints, or traffic density. However, there has been little investigation of individual-differences in lead absorption, distribution, or toxicity, or of genetic causes of such variation. Objectives: We assessed the genetic contribution to variation in blood lead concentration in adults and conducted a preliminary search for genes producing such variation. Methods: Erythrocyte lead concentration was measured by inductively coupled plasma mass spectrometry in venous blood samples from 2,926 Australian adult male and female twins. Mean lead concentrations were compared by place of residence, social class and education, and by the subjects' age, sex, alcohol intake, smoking habits, iron status, and HFE genotype. Results: After adjustment for these covariates, there was strong evidence of genetic effects but not for shared environmental effects persisting into adult life. Linkage analysis showed suggestive evidence (logarithm of odds = 2.63, genome-wide p = 0.170) for a quantitative trait locus affecting blood lead values on chromosome 3 with the linkage peak dose to SLC4A7 a gene whose product affects lead transport. Conclusions: We conclude that genetic variation plays a significant role in determining lead absorption, lead distribution within the body, or both.
AB - Background: Lead is an environmental pollutant that causes acute and chronic toxicity. Surveys have related mean blood lead concentrations to exogenous sources, including industrial activity, use of lead-based paints, or traffic density. However, there has been little investigation of individual-differences in lead absorption, distribution, or toxicity, or of genetic causes of such variation. Objectives: We assessed the genetic contribution to variation in blood lead concentration in adults and conducted a preliminary search for genes producing such variation. Methods: Erythrocyte lead concentration was measured by inductively coupled plasma mass spectrometry in venous blood samples from 2,926 Australian adult male and female twins. Mean lead concentrations were compared by place of residence, social class and education, and by the subjects' age, sex, alcohol intake, smoking habits, iron status, and HFE genotype. Results: After adjustment for these covariates, there was strong evidence of genetic effects but not for shared environmental effects persisting into adult life. Linkage analysis showed suggestive evidence (logarithm of odds = 2.63, genome-wide p = 0.170) for a quantitative trait locus affecting blood lead values on chromosome 3 with the linkage peak dose to SLC4A7 a gene whose product affects lead transport. Conclusions: We conclude that genetic variation plays a significant role in determining lead absorption, lead distribution within the body, or both.
KW - Blood lead
KW - Heritability
KW - Linkage
KW - Toxicogenetics
KW - Twin study
UR - http://www.scopus.com/inward/record.url?scp=34848818008&partnerID=8YFLogxK
U2 - 10.1289/ehp.8847
DO - 10.1289/ehp.8847
M3 - Article
C2 - 17687451
AN - SCOPUS:34848818008
SN - 0091-6765
VL - 115
SP - 1224
EP - 1230
JO - Environmental Health Perspectives
JF - Environmental Health Perspectives
IS - 8
ER -