Bradley E. Aouizerat

Faculty

Bradley E. Aouizerat headshot

Bradley E. Aouizerat

PhD

Professor, College of Dentistry

Bradley E. Aouizerat's additional information

BS, Microbiology/ Molecular Genetics - University of California at Los Angeles
PhD, Microbiology/ Molecular Genetics/lmmunology - University of California at Los Angeles
MAS, Master of Advance Science Research in Clinical - University of California at San Francisco

Oral-systemic health

American Heart Association
American Liver Foundation
American Pain Society
American Society for Human Genetics
International Association for the Study of Pain

Faculty Honors Awards

Excellence in Research Mentoring Faculty Teaching Award (2013)
Excellence in Research Mentoring Faculty Teaching Award (Nominee) (2012)
Excellence in Research Mentoring Faculty Teaching Award (Nominee) (2011)
Most Dedicated Mentor Award, PMCTR Fellowship Program (2009)
Early Career Investigator Award, Bayer Healthcare International (2006)
Multidisciplinary Clinical Research Scholar, Roadmap K12 (2006)
Early Career Faculty Award, Hellman Family (2005)
Faculty Mentorship Award Nominee (2005)
Young Investigator Award, National Hemophilia Foundation (2005)
National Liver Scholar Award, American Liver Foundation (2004)
Irvine H. Page Young Investigator Award (Finalist), American Heart Association (2004)
Faculty Mentorship Award Nominee (2004)
Sam and Rose Gilbert Fellowship, UCLA (1998)
Warsaw Fellowship (1998)

Publications

Newly mapped gene for thoracic aortic aneurysm and dissection

Wung, S. F., & Aouizerat, B. E. (2004). Journal of Cardiovascular Nursing, 19(6), 409-416. 10.1097/00005082-200411000-00013
Abstract
Abstract
Thoracic aortic aneurysm and dissection (TAAD) is associated with high mortality and medical expense. These poor outcomes are preventable by surgical repair; however, identifying at-risk individuals is difficult. Researchers are actively surveying the human genome (the repository of human genes) to characterize the genetic determinants of TAAD by identifying chromosomal regions likely to harbor such predisposing genes. In previous studies, investigators identified genetic markers shared by a subset of families who were ascertained to have the disease, which clustered into 2 chromosomal regions: 5q13-q15 (TAAD1) and 11q23.2-q24 (familial aortic aneurysm [FAA1]). In a subsequent study, a third chromosomal region at 3p24-25 (TAAD2) was found to contribute to TAAD in a 4-generation, 52-member family that displayed little evidence of sharing either the TAAD1 or FAA1 regions. Although additional regions of the genome may contribute to TAAD, investigators are focusing their efforts on identifying the actual genes and the specific mutations that participate in the disease process. The goal of these endeavors is to develop screening tests to identify individuals at risk for familial TAAD. This genetic discovery has significant clinical implications because high-risk individuals and families can be closely monitored and can benefit from preventative surgical repairs.

Novel genetic markers for structural coronary artery disease, myocardial infarction, and familial combined hyperlipidemia: Candidate and genome scans of functional SNPs

Kane, J. P., Aouizerat, B. E., Luke, M. M., Shiffman, D., Iakoubova, O., Liu, D., Rowland, C. M., Catanese, J. J., Leong, D. U., Lau, K. F., Louie, J. Z., Tong, C. H., McAllister, L. B., Dabby, L. F., Ports, T. A., Michaels, A. D., Zellner, C., Pullinger, C. R., Malloy, M. J., & Devlin, J. J. (2004). International Congress Series, 1262, 309-312. 10.1016/j.ics.2003.11.002
Abstract
Abstract
Association studies were conducted on a large number of single nucleotide polymorphisms (SNPs) in pooled screening for association with angiographically determined coronary artery disease (CAD) and myocardial infarction (MI), followed by individual genotyping of those showing association. Forty-seven SNPs showed association with severity of CAD in a replication study applying individual genotyping in 1250 patients. Case control analysis of 340 patients with MI and 300 controls revealed significant associations of three novel genes: an immune cell receptor on chromosome 20p (p=0.02), a zinc finger protein on chromosome 3 (p=0.04), and an unknown gene on chromosome 3 (p=0.01). Associations of polymorphisms in three genes with the phenotype of familial combined hyperlipidemia (FCH), Apo A-V, PPAR alpha and microsomal triglyceride transfer protein (MTP) were established, supporting a metabolic model for the disorder based on misdirection of fatty acid metabolism. Congruence of SNP associations in non-alcoholic steatohepatitis suggests overlap of this syndrome with FCH.

Apolipoprotein A-II: Active or passive role in familial combined hyperlipidemia

Aouizerat, B. E., & Kane, J. P. (2003). Circulation Research, 92(11), 1179-1181. 10.1161/01.RES.0000078362.26826.40

Apolipoprotein a-v: A determinant of plasma triglyceride levels

Aouizerat, B., & Kane, J. (2003). Atherosclerosis.

Gender and ethnic differences in a case-control study of dyslipidemia: using the apolipoprotein A-V gene as an exemplar in cardiovascular genetics.

Wung, S. F., & Aouizerat, B. E. (2003). Research and Theory for Nursing Practice, 17(4), 281-299; discussion 335. 10.1891/rtnp.17.4.281.53189
Abstract
Abstract
Common, complex genetic disorders such as coronary heart disease (CHD) frequently show large population differences, contributing to health disparities. It is also well known that CHD risk factor profiles and the frequency of coronary events differ by gender. Study of premature CHD has revealed that apolipoproteins are important discriminating factors for distinguishing individuals with CHD. Recent findings indicated that apolipoprotein A-V (APOA-V) gene promoter polymorphisms are an important determinant of plasma triglycerides (TG) and lipoprotein cholesterol, and a risk factor for CHD. Variations in APOA-V may have varying impacts in different ethnic groups. The purpose of this interdisciplinary genetic research project was to determine (1) the association of the APOA-V polymorphisms with lipoprotein profiles, and (2) the gender and ethnic differences in the T-1131C promoter polymorphism of the APOA-V gene in individuals with dyslipidemia versus controls. Results indicate that the minor -1131C allele (CC homozygotes + CT heterozygotes) was associated with elevated plasma TG (p = 0.007), very low density lipoprotein (VLDL)-TG (p = 0.019), LDL-TG (p = 0.004), high-density-lipoprotein (HDL)-TG (p < 0.001), and VLDL-cholesterol (p = 0.008). We found a striking elevation in the frequency of the minor C allele in Asians (p < 0.001) compared to Europeans. We also found a significant difference in genotype frequency between men and women in Asians (p = 0.031) and Europeans (p < 0.01). Remarkably, Asian women with the C allele have a 36% increase in TG compared to Asian women homozygous for the T allele. In summary, we found significant ethnic-specific and gender-based differences in the frequency of the minor allele of the -1131 APOA-V gene promoter polymorphism. Identification of genetic variations among ethnic groups and between genders may have significant potential for a better understanding of the development of cardiovascular disease.

Genetic analysis of a polymorphism in the human apoA-V gene: Effect on plasma lipids

Aouizerat, B. E., Kulkarni, M., Heilbron, D., Drown, D., Raskin, S., Pullinger, C. R., Malloy, M. J., & Kane, J. P. (2003). Journal of Lipid Research, 44(6), 1167-1173. 10.1194/jlr.M200480-JLR200
Abstract
Abstract
Recent discovery and characterization of APOAV suggests a role in metabolism of triglyceride (TG)-rich lipoproteins. Previously, variation at the APOAV locus was shown to modestly influence plasma TGs in normolipidemic samples. The aims of this study were to assess the effects of a polymorphism in APOAV (T-1131C) in terms of its frequency among three dyslipidemic populations and a control population, differences of allele frequency across available ethnic groups, and associations with specific lipoprotein TG and cholesterol compartments. We found a striking elevation in the frequency of the rare allele in a Chinese population (P = 0.0002) compared with Hispanic and European populations. The rare allele of the polymorphism was associated with elevated plasma TG (P = 0.012), VLDL cholesterol (P = 0.0007), and VLDL TG (P = 0.012), LDL TG (P = 0.003), and HDL TG (P = 0.016). Linear regression models predict that possession of the rare allele elevates plasma TG by 21 mg/dl (P = 0.009) and VLDL cholesterol by 8 mg/dl (P = 0.0001), and reduces HDL cholesterol by 2 mg/dl (P = 0.017). The association of the polymorphism with altered lipoprotein profiles was observed in combined hyperlipidemia, hypoalphalipoproteinemia, and hyperalphalipoproteinemia, and in controls. These findings indicate that APOAV is an important determinant of plasma TG and lipoprotein cholesterol, and is potentially a risk factor for cardiovascular disease.

Genome scan for blood pressure in Dutch dyslipidemic families reveals linkage to a locus on chromosome 4p

Allayee, H., De Bruin, T. W. A., Dominguez, K. M., Cheng, L. S. C., Ipp, E., Cantor, R. M., Krass, K. L., Keulen, E. T. P., Aouizerat, B. E., Lusis, A. J., & Rotter, J. I. (2001). Hypertension, 38(4), 773-778. 10.1161/hy1001.092617
Abstract
Abstract
Genes contributing to common forms of hypertension are largely unknown. A number of studies in humans and in animal models have revealed associations between insulin resistance, dyslipidemia, and elevated hypertension. To identify genes contributing to blood pressure (BP) variation associated with insulin-resistant dyslipidemia, we conducted a genome-wide scan for BP in a set of 18 Dutch families exhibiting the common lipid disorder familial combined hyperlipidemia. Our results reveal a locus on chromosome 4 that exhibits a significant lod score of 3.9 with systolic BP. In addition, this locus also appears to influence plasma free fatty acid levels (lod=2.4). After adjustment for age and gender, the lod score for systolic BP increased to 4.6, whereas the lod score for free fatty acid levels did not change. The chromosome 4 locus contains an attractive candidate gene, α-adducin, which has been associated with altered BP in animal studies and in some human populations. However, we found no evidence for an association between 2 intragenic α-adducin polymorphisms and systolic BP in this sample. We also observed suggestive evidence for linkage (lod=1.8) of diastolic BP to the lipoprotein lipase gene locus on chromosome 8p, supporting a finding previously observed in a separate insulin-resistant population. In addition, we also obtained suggestive evidence for linkage of systolic BP (lod=2.4) and plasma apolipoprotein B levels (lod=2.0) to a locus on proximal chromosome 19p. In conclusion, our genome scan results support the existence of multiple genetic factors that can influence both BP and plasma lipid parameters.

Analysis of hABC1 gene 5' end: Additional peptide sequence, promoter region, and four polymorphisms

Pullinger, C. R., Hakamata, H., Duchateau, P. N., Eng, C., Aouizerat, B. E., Cho, M. H., Fielding, C. J., & Kane, J. P. (2000). Biochemical and Biophysical Research Communications, 271(2), 451-455. 10.1006/bbrc.2000.2652
Abstract
Abstract
Evidence linking mutations in ATP-binding-cassette transporter gene 1 (ABC1) to Tangier disease suggests it functions in the active transport of free cholesterol out of cells. Since its mRNA level is regulated in response to cellular cholesterol stores it is of interest to explore its promoter response elements, and to investigate polymorphisms for their contributions to the prevalence of low levels of HDL in the population that promotes premature coronary heart disease. Investigation of the 5' end of the gene by 5' RACE analysis revealed 455 nucleotides additional to published sequences, and predicts another 60 amino acid N-terminal residues, resulting in a 2261-residue protein. Protein sequence analysis predicts a membrane-spanning region and possible signal peptide. The 5' flanking region was located by a Human Research Project BLAST search. This region contains regulatory elements that potentially control ABC1 gene expression. In addition to numerous SP1 binding sites there are four putative sterol regulatory elements (SREs). Our studies uncovered three single nucleotide substitution polymorphisms, one in the promoter region and two in the 5' untranslated region (5' UTR), plus an insertion/deletion polymorphism. (C) 2000 Academic Press.

Contribution of the hepatic lipase gene to the atherogenic lipoprotein phenotype in familial combined hyperlipidemia

Allayee, H., Dominguez, K. M., Aouizerat, B. E., Krauss, R. M., Rotter, J. I., Lu, J., Cantor, R. M., De Bruin, T. W. A., & Lusis, A. J. (2000). Journal of Lipid Research, 41(2), 245-252.
Abstract
Abstract
Familial combined hyperlipidemia (FCH) is a common genetic lipid disorder with a frequency of 1-2% in the population. In addition to the hypercholesterolemia and/or hypertriglyceridemia that affected individuals exhibit, small, dense LDL particles and decreased HDL-cholesterol levels are traits frequently associated with FCH. Recently, we reported that families with FCH and families enriched for coronary artery disease (CAD) share genetic determinants for the atherogenic lipoprotein phenotype (ALP), a profile presenting with small, dense LDL particles, decreased HDL-cholesterol levels, and increased triglyceride levels. Other studies in normolipidemic populations have shown that the hepatic lipase (HL) gene is linked to HDL- cholesterol levels and that a polymorphism within the HL promoter (-514C→T) is associated with increased HDL-cholesterol levels as well as larger, more buoyant LDL particles. In the present study, we tested whether the HL, gene locus also contributes to ALP in a series of Dutch FCH families using nonparametric sibpair linkage analysis and association analysis. Evidence for linkage of LDL particle size (P < 0.019), HDL-cholesterol (P < 0.003), and triglyceride levels (P < 0.026) to the HL gene locus was observed. A genome scan in a subset of these families exhibited evidence for linkage of PPD (LOD = 2.2) and HDL-cholesterol levels (LOD = 1.2) to the HL gene locus as well. The -514C→T promoter polymorphism was significantly associated (P < 0.0001) with higher HDL-cholesterol levels in the unrelated males of this population, but not in unrelated females. No association was observed between the polymorphism and LDL particle size or triglyceride levels. Our results provide support that ALP is a multigenic trait and suggest that the relationship between small, dense LDL particles, HDL-cholesterol, and triglyceride levels in FCH families is due, in part, to common genetic factors.

Genome scan for adiposity in Dutch dyslipidemic families reveals novel quantitative trait loci for leptin, body mass index and soluble tumor necrosis factor receptor superfamily 1A

Van Der Kallen, C. J. H., Cantor, R. M., Van Greevenbroek, M. M. J., Geurts, J. M. W., Bouwman, F. G., Aouizerat, B. E., Allayee, H., Buurman, W. A., Lusis, A. J., Rotter, J. I., & De Bruin, T. W. A. (2000). International Journal of Obesity, 24(11), 1381-1391. 10.1038/sj.ijo.0801412
Abstract
Abstract
OBJECTIVE: To search for novel genes contributing to adiposity in familial combined hyperlipidemia (FCH), a disorder characterized by abdominal obesity, hyperlipidemia and insulin resistance, using a 10 cM genome-wide scan. DESIGN: Plasma leptin and soluble tumor necrosis factor receptor superfamily members 1A and 1B (sTNFRSF1A and sTNFRSF1B, also known as sTNFR1 and sTNFR2) were analyzed as unadjusted and adjusted quantitative phenotypes of adiposity, in addition to body mass index (BMI), in multipoint and single-point analyses. In the second stage of analysis, an important chromosome 1 positional candidate gene, the leptin receptor (LEPR), was studied. SUBJECTS: Eighteen Dutch pedigrees with familial combined hyperlipidemia (FCH) (n=198) were analyzed to search for chromosomal regions harboring genes contributing to adiposity. RESULTS: Multipoint analysis of the genome scan data identified linkage (log of odds, LOD, 3.4) of leptin levels to a chromosomal region defined by D1S3728 and D1S1665, flanking the leptin receptor (LEPR) gene by approximately 9 and 3 cM, respectively. The LOD score decreased to 1.8 with age- and gender-adjusted leptin levels. Notably, BMI also mapped to this region with an LOD score of 1.2 (adjusted BMI: LOD 0.5). Two polymorphic DNA markers in LEPR and their haplotypes revealed linkage to unadjusted and adjusted BMI and leptin, and an association with leptin levels was found as well. In addition, the marker D8S1110 showed linkage (LOD 2.8) with unadjusted plasma concentrations of soluble TNFRSF1A. BMI gave a LOD score of 0.6. Moreover, a chromosome 10q-ter locus, AFM198ZB, showed linkage with adjusted BMI (LOD 3.3). CONCLUSION: These data provide evidence that a human chromosome 1 locus, harboring the LEPR gene, contributes to plasma leptin concentrations, adiposity and body weight in humans affected with this insulin resistant dyslipidemic syndrome. Novel loci on chromosome 8 and 10qter need further study.