Hyperhomocysteinemia, a condition of elevated plasma homocysteine concentration resulting from impaired sulfur amino acid metabolism, may be a powerful risk factor for occlusive vascular disease. However, little is known about the distribution of homocysteine levels or the prevalence of hyperhomocysteinemia in the general population. The possibility of racial differences in homocysteine distribution has not been considered, nor have age-related differences in homocysteine concentrations been measured across the entire adult age range in the same population. Furthermore, a number of possible determinants of plasma homocysteine concentration have been identified, but their importance at a population level has received little study. The investigators' previous application (R01-HL52630-02) allowed them to begin to address these questions in adult and adolescents. However, there is essentially no knowledge of the distribution and determinants of homocysteine levels in representative samples of children. The investigators' preliminary data suggest dramatic differences in homocysteine concentration with age even among adolescents. The present application seeks to extend this study to children age 4-11 years. This will not only allow the investigators to characterize normal homocysteine concentrations among children, but to identify nutritional and non-nutritional determinants of total homocysteine concentrations in children. To examine these issues, the Centers for Disease Control and Prevention (CDC) has provided the investigators with surplus serum specimens from approximately 2,000 children ages 4 to 11 years who participated in the second phase of the third National Health and Nutrition Examination Survey (NHANES III) so that they can perform the following tasks: 1) measure total serum homocysteine concentration in 2,045 serum samples from phase 2 of NHANES III to describe the distribution of total serum homocysteine concentrations and prevalence of elevated homocysteine in the U.S. among white, African-American and Mexican-American boys and girls aged 4 to 11 years, and test for differences in mean homocysteine concentrations and prevalence of hyperhomocysteinemia among race/ethnicity, sex and age categories; 2) identify possible determinants of serum homocysteine concentrations in children aged 4 to 11 years, with a focus on the influence of body size; and 3) relate RBC folate and serum folate and vitamin B12 levels to homocysteine concentration to identify levels of these nutrients required to achieve minimum homocysteine concentrations, and ascertain the proportion of elevated homocysteine in American children that can be attributed to inadequate vitamin status.
