Biomedical subjects

Jeff T Williams

Publications and source records attributed to Jeff T Williams.

22 records · Page 2Linked to original sources

PubMed2002

Genetic basis of variation in carotid artery plaque in the San Antonio Family Heart Study.

BACKGROUND AND PURPOSE: In contrast to the commonly used quantitative marker of subclinical atherosclerosis, namely intima-media thickness, we investigated the extent to which the presence or absence of carotid artery plaque (CAP) was under genetic control. METHODS: The study population consisted of 750 individuals distributed across 29 randomly ascertained extended Mexican American pedigrees who participated in the second examination cycle of the San Antonio Family Heart Study. Extracranial focal CAP was identified by B-mode ultrasound bilaterally in the internal carotid artery or the carotid bulb. Using a variance decomposition approach implemented in the SOLAR computer program, we performed genetic analysis on the discrete trait CAP (ie, liability to disease) using a threshold model. Covariates considered in the analysis included age, sex, diabetes, current smoking status, lipid levels, and markers of hypertension and obesity. RESULTS: Fifty-one of 461 women and fifty-seven of 289 men with a mean age of 42.1 years had evidence of a plaque in the right and/or left carotid artery. The age- and sex-adjusted heritability (h(2)+/-SE) for CAP was significant (h(2)=0.28+/-0.15, P=0.01). Furthermore, after adjustment for additional covariates that contributed significantly to the model (P<0.05; diabetes, hypertension, body mass index, waist circumference, and smoking status), heritability remained significant (h(2)=0.23+/-0.15, P=0.03). CONCLUSIONS: Our data indicate that after established cardiovascular risk factors are controlled for, the variation of the discrete trait CAP is under appreciable additive genetic influences.

Adolescent↗

PubMed2002

Linkage for platelet monoamine oxidase (MAO) activity: results from a replication sample.

BACKGROUND: Monoamine oxidase B (MAO-B) degrades catecholamines in presynaptic nerve endings and is also active in platelets. There is evidence to suggest that platelet MAO-B activity level is controlled by a major genetic locus distinct from the structural gene on the X chromosome. To expand on a prior report, new linkage analyses for platelet MAO-B activity have been performed on the previously analyzed sample (designated the initial sample), on a new sample of families (the replication sample), and on the combined sample. These families were recruited as part of the Collaborative Study on the Genetics of Alcoholism (COGA). METHODS: The initial sample consists of 105 extended families providing 1002 nonindependent (412 independent) sib pairs that have been phenotyped for MAO activity and genotyped. The replication sample of 157 extended families contains 608 nonindependent (309 independent) phenotyped and genotyped sib pairs. Analyses were conducted using Haseman-Elston based regression on sib pairs and variance component analysis on extended pedigrees, and the importance of cigarette smoking and gender as covariates of platelet MAO-B activity was taken into account. RESULTS: Regions on chromosomes 2, 9, and 12 indicated consistent evidence for linkage across the two distinct datasets by at least one analysis method. Under Haseman-Elston regression of independent sib pairs, only the chromosome 2 region gave lod scores above 1 in both the initial and replication samples. Using all possible pairs, unweighted, for the regression, chromosome 12 gave lod scores above 1 in both samples. For variance component analysis, only the chromosome 9 region gave lod scores above 1 in both samples. CONCLUSIONS: The consistency across datasets of these findings is encouraging. In particular, variance component analysis of extended pedigrees supports a potential linkage of MAO-B activity to chromosome 9, with a lod over 3 at 115 cM near D9S261 in the combined sample. Sib-pair regression supports this finding with modest lod scores in the region. Suggestive linkage to chromosomes 2 and 12 from sib-pair analysis is only weakly supported by variance component analysis.

Blood Platelets↗

PubMedDate not supplied

Evidence for distinct genetic effects on obesity and lipid-related CVD risk factors in diabetic compared to nondiabetic American Indians: the Strong Heart Family Study.

BACKGROUND: The relationship between diabetes and increased cardiovascular disease (CVD) risk is well established. Previous data from the Strong Heart Family Study (SHFS) have demonstrated significant heritabilities for CVD risk factors and implicated diabetes as an important predictor of several of the phenotypes in three large groups of American Indians in Arizona (AZ), Oklahoma (OK), and the Dakotas (DK). However, the genetic architecture of this relationship is not well understood. The purpose of the present paper is to determine whether the genetic effects on CVD risk factors in the SHFS are different in diabetic and nondiabetic individuals. METHODS: Approximately 950 men and women, 18 years or older, in 32 extended families, were examined between 1997 and 1999. Interaction between genotype and diabetes status was estimated for nine CVD risk factors [body fat mass (FAT), body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), log-transformed fibrinogen, log-transformed triglycerides, log-transformed urinary albumin : creatinine ratio (LACR), plasminogen activator inhibitor 1 (PAI-1), systolic blood pressure (SBP), and waist-to-hip ratio (WHR)], using a maximum likelihood variance decomposition technique. RESULTS: We found evidence that genetic factors influencing BMI, FAT, log-transformed triglycerides, HDL-C, and WHR are differentially expressed in individuals with diabetes compared to those without diabetes. CONCLUSION: Thus, in the environmental and genetic milieu of diabetes, there may be distinct genetic determinants of various CVD risk factors.

Aged↗

PubMedDate not supplied

Myocardial contrast echocardiography in assessing microcirculation in baboons with chagas disease.

OBJECTIVE: Microvascular abnormalities have been postulated in the pathogenesis of chagasic cardiomyopathy. The objective of this study was to evaluate the relationship between coronary microcirculation and systolic function impairment in baboons with Chagas disease using myocardial contrast echocardiography (MCE). METHODS: Seventeen seropositive (5 males, 12 females; mean age 20 years) and 13 age- and gender-matched seronegative baboons underwent MCE using intravenous octafluoropropane human albumin microspheres. Color-coding was used to enhance tissue contrast in assessing regional myocardium uniformity and texture. Dipyridamole (0.54 mg/kg) was given to a subset of 4 animals to challenge coronary flow reserve. Systolic indices included left ventricular fractional shortening, velocity of circumferential fiber shortening, and left and right ventricular ejection fractions. RESULTS: Four of the 17 (24%) seropositive primates had decreased fractional shortening (25 +/- 8% vs. 40 +/-5%, p <.005), velocity of circumferential fiber shortening (1.05 +/- 0.36 circ/s vs. 1.84 +/- 0.23 circ/s, p <.0001), and reduced right ventricular ejection fraction (44 +/- 9% vs. 54 +/- 4%, p <.05) compared to other seropositive animals. Seropositive and seronegative groups showed no significant differences on the coronary microcirculation pattern as evaluated by MCE, including the 4 baboons with systolic function impairment. Moreover, coronary flow vasoreactivity resulted in a significant increase in myocardial flow as detected by color-coding masking. CONCLUSIONS: Chagasic heart disease is present in 24% of seropositive baboons spontaneously infected with Trypanosoma cruzi. MCE reveals a discrepancy between coronary microcirculation at rest and alterations in myocardial contractility, suggesting preservation of the microvascular integrity in this unique animal model.

Albumins↗