Evidence of genetic effects on blood lead concentration.
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.


OBJECTIVE
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 close 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.
Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, Australia. John.Whitfield@email.cs.nsw.gov.au
John B
JB
Whitfield
Veronica
V
Dy
Robert
R
McQuilty
Gu
G
Zhu
Grant W
GW
Montgomery
Manuel A R
MA
Ferreira
David L
DL
Duffy
Michael C
MC
Neale
Bas T
BT
Heijmans
Andrew C
AC
Heath
Nicholas G
NG
Martin
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D001315:Australia; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D004785:Environmental Pollutants / Q000097:blood*; D005260:Female; D005293:Ferritins / Q000097:blood; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007501:Iron / Q000097:blood; D007854:Lead / Q000097:blood*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D040641:Quantitative Trait Loci; D027982:Sodium-Bicarbonate Symporters / Q000235:genetics; D014168:Transferrin / Q000378:metabolism; D014427:Twins / Q000097:blood / Q000235:genetics*; D014527:Uric Acid / Q000097:blood
D004785:Environmental Pollutants; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; C422022:SLC4A7 protein, human; D027982:Sodium-Bicarbonate Symporters; D014168:Transferrin; D014527:Uric Acid; D007854:Lead; D005293:Ferritins; D007501:Iron