Modification by ALAD of the Association between Blood Lead and Blood Pressure in the U.S. Population: Results from the Third National Health and Nutrition Examination Survey

BACKGROUND: Environmental lead exposure has been found to be associated with an increased risk of hypertension. Individuals vary greatly in susceptibility to lead toxicity, and genetic susceptibility has often been cited as the probable cause for such variation. OBJECTIVE: The main objective is to determine the role of the aminolevulinic acid dehydratase (ALAD) gene, which encodes the main carrier protein of lead in blood, in the association between lead exposure and blood pressure (BP) and hypertension in the U.S. population. METHODS: We analyzed data from individuals ≥ 17 years of age who participated in the Third National Health and Nutrition Examination Survey for whom DNA was available (n = 6,016). Multivariable logistic and linear regressions stratified by race/ethnicity were used to examine whether hypertension and BP were associated with ALAD and blood lead levels (BLL). RESULTS: BLL was associated with systolic BP in non-Hispanic whites and with hypertension and systolic and diastolic BP in non-Hispanic blacks. BLL was not associated with BP outcomes in Mexican Americans. Non-Hispanic white ALAD2 carriers in the highest BLL quartile (3.8–52.9 μg/dL) had a significantly higher adjusted prevalence odds ratio for hypertension compared with ALAD1 homozygous individuals. We also found a significant interaction between lead concentration and the ALAD2 allele in non-Hispanic whites and non-Hispanic blacks in relation to systolic BP. CONCLUSIONS: BLL may be an important risk factor for hypertension and increased systolic and diastolic BP. These associations may be modified by ALAD genotype.