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. 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 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. KEY WORDS: blood lead, heritability, linkage, toxicogenetics, twin study. Environ Health Perspect 115:1224-1230 (2007). doi:10.1289/ehp.8847 available via http://dx.doi.org/ [Online 14 June 2007] John B. Whitfield, Veronica Dy, Robert McQuilty, Gu Zhu, Grant W. Montgomery, Manuel A.R. Ferreira, David L. Duffy, Michael C. Neale, Bas T. Heijmans, Andrew C. Heath, and Nicholas G. Martin (1)Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, Australia; (2)Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Australia; (3)Department of Psychiatry and Human Genetics, Virginia Commonwealth University, Richmond, Virginia, USA; (4)Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; (5)Missouri Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA
Many elements and compounds present in the environment pose significant health risks to exposed individuals, and contribute to the burden of disease for society. For any exposed person the outcome [...]