Good Gene Hunting: University of Pittsburgh Researchers to Look for Genetic Influences on HDL Cholesterol

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health has awarded a $2.9 million grant to researchers at the University of Pittsburgh’s Graduate School of Public Health (GSPH) to uncover the genetic basis of high-density lipoprotein (HDL) cholesterol, the so-called “good cholesterol,” in African and U.S. white populations.

Higher levels of HDL have been shown to provide protection against the risk of coronary heart disease (CHD). Generally, African or African-derived populations have higher HDL levels than whites, which may ameliorate the risk of CHD among Africans. In Africa, CHD is near absent in rural areas, and very uncommon in urban centers.

According to principal investigator M. Ilyas Kamboh, Ph.D., professor and acting chair of the department of human genetics at GSPH, blood HDL cholesterol levels are determined both by environmental and genetic factors, with genes contributing more than 50 percent.

“The task of identifying underlying genetic factors is not easy because there are multiple genes involved as well as interactions between genes and the environment. All of these have to be factored into studies to determine what contributes to variation in plasma HDL cholesterol levels between individuals and populations,” Dr. Kamboh explained.

He said that most of the past efforts to identify genes for HDL cholesterol have been focused on screening for a few selected single nucleotide polymorphisms (SNPs) per each potential candidate gene, which is not optimal. However, the recent availability of high-throughput DNA sequencing technology has provided researchers the tools they need to build “dense” maps of markers for each gene being examined.

“These maps, which we will make for each defined population in our study, will allow us to complete a much more thorough examination of the role of variation in genes that influence HDL cholesterol than we would by scanning for SNPs,” said Dr. Kamboh.

In all, the four-year study will sequence more than 40 candidate genes from individuals who have extremely high or low HDL levels in order to find significant genetic variations. According to Dr. Kamboh, the successful completion of this study may lead to the identification of genetic variants that either decrease or increase the risk of CHD via HDL cholesterol in the general population, which could then become targets for drugs that can regulate these genes.

In addition to Dr. Kamboh, other GSPH researchers involved in the project include Yesim Demirci, M.D. and Candace Kammerer, Ph.D. of the department of human genetics and Clareann Bunker, Ph.D. of the department of epidemiology.

Founded in 1948 and fully accredited by the Council on Education for Public Health, GSPH is world-renowned for contributions that have influenced public health practices and medical care for millions of people. One of the top-ranked schools of public health in the United States, GSPH was the first fully accredited school of public health in the Commonwealth of Pennsylvania, with alumni who are among the leaders in their fields of public health. A member of the Association of Schools of Public Health, GSPH currently ranks third among schools of public health in National Institutes of Health funding received. The only school of public health in the nation with a chair in minority health, GSPH is a leader in research related to women’s health, HIV/AIDS and human genetics, among others. For more information about GSPH, visit the school’s Web site at http://www.publichealth.pitt.edu.