Showing papers by "John H. Eckfeldt published in 2000"
TL;DR: The Hypertension Genetic Epidemiology Network (HyperGEN) as discussed by the authors is a family-based network of researchers who seek to identify and characterize genes promoting hypertension, a major contributor to cardiovascular morbidity and mortality.
166 citations
TL;DR: Serum albumin was inversely associated with incident CHD at the baseline examination in current smokers but not in never or former smokers, and may be a marker of susceptibility to the inflammatory response that results from smoking.
Abstract: Various studies have reported an inverse association between serum albumin level and incident coronary heart disease (CHD), though biologic mechanisms have not been established. The authors examined the association between serum albumin level and CHD in the Atherosclerosis Risk in Communities cohort, comprising 14,506 White and African-American middle-aged men and women. The mean albumin level in this population was 3.9 g/dl (standard deviation 0.3). During 5.2 years of follow-up, 470 incident CHD events occurred. The hazard ratio for incident CHD associated with a 1-standard deviation decrease in serum albumin level was 1.26 (95% confidence interval (CI): 1.15, 1.38) after adjustment for age, gender, and ethnicity and 1.18 (95% CI: 1.07, 1.30) after additional adjustment for covariates related to CHD. Hazard ratios were similar across gender and ethnic groups. However, there was statistically significant effect modification by smoking status, with hazard ratios of 1.01 (95% CI: 0.84, 1.22) among never smokers, 1.09 (95% CI: 0.92, 1.30) among former smokers, and 1.35 (95% CI: 1.17, 1.54) among current smokers. Further adjustment for factors related to renal disease, nutrition, platelet aggregation, inflammation, use of angiotensin-converting enzyme inhibitors, and hemostasis factors attenuated the albumin-CHD relation only slightly. In this study, serum albumin was inversely associated with incident CHD at the baseline examination in current smokers but not in never or former smokers. Albumin level may be a marker of susceptibility to the inflammatory response that results from smoking.
132 citations
TL;DR: The hypothesis that uric acid is a multifactorial trait possibly influenced by more than one major gene, modifying genes, and environmental factors is supported.
Abstract: Segregation analysis was performed on the serum uric acid measurements from 523 randomly ascertained Caucasian families from the NHLBI Family Heart Study. Gender-specific standardized residuals were used as the phenotypic variable in both familial correlation and segregation analysis. Uric acid residuals were adjusted for age, age2, age3, body mass index (kg/m2), creatinine level, aspirin use (yes/no), total drinks (per week), HOMA insulin resistance index [(glucose * insulin)/22.5], diuretic use (yes/no), and triglyceride level. Sibling correlations (r=0.193) and parent-offspring correlations (r=0.217) were significantly different from zero, but these two familial correlations were not significantly different from one another. After adjustment for covariates, the heritability estimate for serum uric acid was 0.399. Segregation analysis rejected the "no major gene" model but was unable to discriminate between an "environmental" and a "Mendelian major gene" model. These results support the hypothesis that uric acid is a multifactorial trait possibly influenced by more than one major gene, modifying genes, and environmental factors.
78 citations
TL;DR: The α-adducin gene remained a significant independent predictor of hypertension in a multivariate logistic model even after correcting for other risk factors for hypertension, including gender, age, body mass index (BMI), smoking, LDL cholesterol, triglycerides, urine sodium (Na), and urine potassium (K), and through the use of regression trees, several gene-by-environment interactions were implicated.
62 citations
TL;DR: The present finding of a positive association between tHcy and intimal-medial wall thickness strengthens the in vitro finding of the stimulating effect of homocysteine on vascular smooth muscle cell growth, which may be an important mechanism through which mildly elevated plasma tHCy promotes atherosclerosis.
46 citations
TL;DR: The genetic background of Lewis negative blood group phenotype and its association with atherosclerotic disease in the NHLBI Family Heart Study is studied.
Abstract: . Salomaa V, Pankow J, Heiss G, Cakir B, Eckfeldt JH, Ellison RC, Myers RH, Hiller KM, Brantley KR, Morris TL, Weston BW (National Public Health Institute, Helsinki, Finland, University of North Carolina, University of Minnesota, Boston University School of Medicine, USA). Genetic background of Lewis negative blood group phenotype and its association with atherosclerotic disease in the NHLBI Family Heart Study, J Intern Med 2000; 247: 689–698.
Objectives. To examine the prevalence of four mutations, T59G, T1067A, T202C and C314T, of the human α(1,3/1,4) fucosyltransferase 3 (FUT 3) gene amongst persons with Lewis negative and those with Lewis positive blood group phenotype. An additional objective was to explore the hypothesis that these mutations are associated with coronary heart disease and inflammatory reaction.
Design. A population-based cross-sectional study.
Setting. Analysis of samples and data from the National Heart Lung and Blood Institute Family Heart Study.
Subjects. All Lewis (a–b–) participants (n = 136) and a sample of Lewis positive participants (n = 136) of the Family Heart Study; all were of Caucasian ethnicity.
Main outcome measures. The prevalence of examined mutations by Lewis phenotype.
Results. The examined mutations were common and strongly associated with the Lewis (a–b–) phenotype. Accordingly, 90–95% of Lewis (a–b–) individuals amongst Caucasians can be identified by screening for these four mutations. Exploratory analyses suggested that with the exception of T59G, all examined mutations were positively associated with prevalent coronary heart disease, although not statistically significantly, perhaps due to the small number of prevalent coronary heart disease cases. C-reactive protein tended to be higher amongst persons with a TC or CC genotype at position 202 (3.07 ± 0.41 vs. 2.08 ± 0.32 mg L–1, P = 0.06).
Conclusions. Four specific mutations of fucosyltransferase 3 gene are responsible for the vast majority of Lewis (a–b–) phenotypes in Caucasians. These mutations are common in the population at large and may be associated with increased risk of coronary heart disease. Further studies using larger samples are warranted.
33 citations
TL;DR: The investigation in the FHS sample of families suggests that there is only a small, if any, influence of insulin levels on BP after adjustment for obesity-related sources of variation.
10 citations
TL;DR: The findings suggest that the ACE insertion/deletion polymorphism has relatively little, if any, influence on circulating PAI-1 levels in the population at large.
Abstract: Experimental and clinical research supports a direct link between activation of the renin-angiotensin system and production of plasminogen activator inhibitor-1 (PAI-1), the primary physiologic inhibitor of tissue plasminogen activator. Several studies have reported higher PAI-1 levels in individuals carrying the deletion (D) allele of the angiotensin-converting enzyme (ACE) gene. We investigated the association between ACE genotypes and plasma PAI-1 levels in a family study of 577 women and 428 men from four US communities. Participants were between 25 and 84 years of age without evidence of coronary heart disease (CHD). Mean geometric plasma PAI-1 levels adjusted for ethnicity were 17.4, 17.9, and 18.1 ng/ml in participants with the DD, insertion-deletion (ID), and II genotypes, respectively (P = 0.89 for difference). We found no associations between ACE I/D genotypes and plasma PAI-1 antigen concentrations in a subset of participants without major CHD risk factors (hypertension, hypercholesterolemia, overweight, smoking, diabetes) or in a small sample of African-Americans. Our findings suggest that the ACE insertion/deletion polymorphism has relatively little, if any, influence on circulating PAI-1 levels in the population at large.
6 citations
TL;DR: In this article, the authors performed linkage analyses between the very low-density lipoprotein (VLDL) receptor gene and fasting insulin and the homeostasis model assessment (HOMA) insulin resistance index (fasting insulin · fasting glucose/225).
Abstract: A major gene effect on the fasting insulin level and insulin resistance has been suggested in previous studies Several candidate genes for insulin resistance in rare syndromes have been proposed However, there has been limited success in finding genes for common forms of insulin resistance There is accumulating evidence of a relationship between insulin resistance and a disturbance of free fatty acid (FFA) metabolism The very—low-density lipoprotein (VLDL) receptor, which is associated with FFA metabolism, could serve as a possible candidate gene for insulin resistance We performed linkage analyses between the VLDL receptor gene and fasting insulin and the homeostasis model assessment (HOMA) insulin resistance index (fasting insulin · fasting glucose/225) in 1,050 sibpairs participating in the phase II physical examination of the National Heart, Lung, and Blood Institute Family Heart Study (FHS) Data analyses were completed using the SIBPAL component of the SAGE software package (SAGE, Statistical Analysis for Genetic Epidemiology, Version 31; Computer program package available from the Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, 1997) We did not find evidence for linkage of the fasting insulin or the HOMA insulin resistance index with a polymorphic marker at the VLDL locus (P = 316 and 402, respectively) Adjustment of fasting insulin and the HOMA insulin resistance index for the body mass index (BMI) did not change the results (P = 319 and 472, respectively) In conclusion, no evidence was found for a linkage between a locus controlling the fasting insulin level or HOMA insulin resistance index and a VLDL polymorphism in the present study Additional adjustment of fasting insulin or the HOMA insulin resistance index for the BMI did not change the linkage results significantly
2 citations