Biomedical subjects

Molly Bray

Publications and source records attributed to Molly Bray.

3 recordsLinked to original sources

PubMed2003

Risk of atherosclerosis: interaction of smoking and glutathione S-transferase genes.

BACKGROUND: Cigarette smoking is a well-known risk factor for not only incident events of coronary heart disease, but also preclinical atherosclerosis. Enzymes including glutathione S-transferase mu (GSTM1) and theta (GSTT1) are involved in the metabolism of tobacco smoke chemicals and are expressed in human vessels and smooth muscle cells. METHODS: We estimated the effect of interaction of smoking with the deletion polymorphisms of GSTM1 and GSTT1 on the risk of carotid artery atherosclerosis. We analyzed a stratified random sample of 1394 individuals from the Atherosclerosis Risk in Communities (ARIC) study, which is a prospective cohort study of 15,792 white and black men and women randomly selected from four U.S. communities between 1987 and 1989. As an index of generalized atherosclerosis, we used carotid artery intimal-medial thickness, as determined by B-mode ultrasound at the baseline or first follow-up examination in asymptomatic individuals. RESULTS: We found a suggestion of an interaction between the functional GSTT-1 genotype (GSTT-1) and heavy smoking. For 20 or more pack-years and GSTT1-1, the odds ratio for increased intimal-medial thickness was 4.7 (95% confidence interval = 1.9-11.8); for 20 or more pack-years and GSTT1-0, 1.7 (0.5-5.5); and for nonsmokers and GSTT1-1, 0.7 (0.3-1.5). We found no interaction between smoking and GSTM1. CONCLUSIONS: The results of this analysis of preclinical atherosclerosis extend reports from the ARIC study of an interaction between smoking and GSTT1-1 in relation to the risk of incident coronary heart disease and lower extremity arterial disease.

Arteriosclerosis↗

PubMed2002

A combined analysis of genomewide linkage scans for body mass index from the National Heart, Lung, and Blood Institute Family Blood Pressure Program.

A combined analysis of genome scans for obesity was undertaken using the interim results from the National Heart, Lung, and Blood Institute Family Blood Pressure Program. In this research project, four multicenter networks of investigators conducted eight individual studies. Data were available on 6,849 individuals from four ethnic groups (white, black, Mexican American, and Asian). The sample represents the largest single collection of genomewide scan data that has been analyzed for obesity and provides a test of the reproducibility of linkage analysis for a complex phenotype. Body mass index (BMI) was used as the measure of adiposity. Genomewide linkage analyses were first performed separately in each of the eight ethnic groups in the four networks, through use of the variance-component method. Only one region in the analyses of the individual studies showed significant linkage with BMI: 3q22.1 (LOD 3.45, for the GENOA network black sample). Six additional regions were found with an associated LOD >2, including 3p24.1, 7p15.2, 7q22.3, 14q24.3, 16q12.2, and 17p11.2. Among these findings, the linkage at 7p15.2, 7q22.3, and 17p11.2 has been reported elsewhere. A modified Fisher's omnibus procedure was then used to combine the P values from each of the eight genome scans. A complimentary approach to the meta-analysis was undertaken, combining the average allele-sharing identity by descent (pi) for whites, blacks, and Mexican Americans. Using this approach, we found strong linkage evidence for a quantitative-trait locus at 3q27 (marker D3S2427; LOD 3.40, P=.03). The same location has been shown to be linked with obesity-related traits and diabetes in at least two other studies. These results (1) confirm the previously reported obesity-susceptibility locus on chromosomes 3, 7, and 17 and (2) demonstrate that combining samples from different studies can increase the power to detect common genes with a small-to-moderate effect, so long as the same gene has an effect in all samples considered.

Adult↗

PubMed2002

LPL polymorphism predicts stroke risk in men.

Variation in lipid levels has been associated with atherosclerotic vascular disease, including stroke. Genes contributing to interindividual variation in lipid levels may play a role in the etiology of stroke, either through their effects on lipid synthesis and metabolism or through separate pathways. For this reason, we sought to examine the association between polymorphisms in the lipoprotein lipase (LPL) and apolipoprotein E (APOE) genes and subclinical and clinical stroke in the Atherosclerosis Risk in Communities (ARIC) Study. Subclinical stroke was determined by cerebral magnetic resonance imaging (MRI). Subclinical cerebral infarct cases (n = 197) were compared to a stratified random sample identified from individuals participating in the MRI examination (n = 200). Incidence of clinical ischemic stroke was determined by following the ARIC cohort for an average of 7.5 years for potential cerebrovascular events; 218 validated clinical ischemic strokes were identified. A stratified random sample of the ARIC cohort (CRS, n = 964) was used as the comparison group for clinical cases. The LPL S291-carrying genotypes and APOE epsilon2- and epsilon4-carrying genotypes were not significantly associated with subclinical or clinical stroke. The LPL X447-containing genotypes were significantly associated with subclinical (odds ratio [OR], 4.32; 95% confidence interval [CI], 1.23-15.15; P = 0.020) and clinical stroke (hazard rate ratio [HRR], 2.57; 95% CI, 1.24-5.34; P = 0.01) in men, both by themselves and after adjustment for multiple stroke risk factors. The LPL S447X polymorphism is significantly associated with subclinical cerebral infarction and incident clinical ischemic stroke in men from a middle-aged American population. This association does not appear to be mediated by triglyceride, high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol levels, or additional stroke risk factors.

Apolipoproteins E↗