The genetic response to short-term interventions affecting cardiovascular function: rationale and design of the Heredity and Phenotype Intervention (HAPI) Heart Study.

BACKGROUND: The etiology of cardiovascular disease (CVD) is multifactorial. Efforts to identify genes influencing CVD risk have met with limited success to date, likely because of the small effect sizes of common CVD risk alleles and the presence of gene by gene and gene by environment interactions. METHODS: The HAPI Heart Study was initiated in 2002 to measure the cardiovascular response to 4 short-term interventions affecting cardiovascular risk factors and to identify the genetic and environmental determinants of these responses. The measurements included blood pressure responses to the cold pressor stress test and to a high salt diet, triglyceride excursion in response to a high-fat challenge, and response in platelet aggregation to aspirin therapy. RESULTS: The interventions were carried out in 868 relatively healthy Amish adults from large families. The heritabilities of selected response traits for each intervention ranged from 8% to 38%, suggesting that some of the variation associated with response to each intervention can be attributed to the additive effects of genes. CONCLUSIONS: Identifying these response genes may identify new mechanisms influencing CVD and may lead to individualized preventive strategies and improved early detection of high-risk individuals.

Concentrations of B vitamins and homocysteine in children with sickle cell anemia.

BACKGROUND: Elevated concentration of serum homocysteine contributes to thrombosis, a frequent event in patients with sickle cell anemia. We aimed to test whether children with sickle cell anemia have elevated concentrations of serum homocysteine with diminished levels of folate or B vitamins from accelerated blood cell turnover. METHODS: We conducted a case-control study of children with homozygous sickle cell anemia (n = 17) and unaffected children (n = 11). We measured serum and red blood cell folate, vitamin B6, vitamin B12, and homocysteine concentrations, and assessed micronutrient intake. RESULTS: Children with sickle cell anemia had concentrations of homocysteine slightly higher than those of unaffected children. They had lower vitamin B6 concentrations and comparable concentrations of folate and vitamin B12. Homocysteine concentration was inversely related to vitamin B12 concentration and was not independently associated with levels of vitamin B6 or folate. CONCLUSION: Despite comparable intake, children with sickle cell anemia had lower concentrations of vitamin B6 than unaffected children. Larger studies are needed to determine if chronically low serum vitamin B6 concentration contributes to hyperhomocysteinemia in this population.