Departmental scientists are investigating the genetic components of heart disease in Mexican Americans; heart disease is the leading cause of death in this population. Over the past two decades, there has been increasing interest in the contribution of genes to risk of heart disease. But nearly all of the genetic research on heart disease has been done in populations of Northern European ancestry. An NHLBI-funded effort in San Antonio is directed at discovering the contribution of genes to heart disease risk in Mexican Americans. The San Antonio Family Heart Study is the only large, population-based genetic study of risk for heart disease in Mexican American families. The San Antonio Family Heart Study is focusing on 1,400 members of more than 40 large Mexican American families in San Antonio. This research effort, which is a collaborative project involving the Texas Biomedical Research Institute and the U.T. Health Science Center at San Antonio, is funded by a Program Project (HL45522) that began in 1991.
The families in the San Antonio Family Heart Study include 40 to 60 year old men and women and their spouses, children, parents, brothers and sisters, grandchildren, aunts and uncles, nieces and nephews, and first cousins. The largest family contains more than 100 examined individuals. We administered a questionnaire to each participant to obtain information on family relationships, demographic characteristics, medical history, and environmental risk factors such as diet, smoking, alcohol use, physical activity, and prescription drug use. Each family member was given a physical examination and blood was drawn for genetic studies. Because non-insulin-dependent diabetes mellitus and obesity have high prevalence in Mexican Americans and may have some of the same underlying genetic determinants as heart disease, the examination included measures of diabetes and obesity as well. In 1997-2002 we re-examined 850 family members to determine whether other precursors and risk factors, such as carotid artery wall thickness and clotting phenotypes, are genetically determined. We are now doing a third examination in order to assess additional risk factors for cardiovascular disease, diabetes, and obesity.
We have found evidence for numerous major genes that influence risk of heart disease, diabetes, or obesity. One of the genes has a large effect on fat mass; one influences insulin levels; one influences the level of leptin, which is involved in satiety; and still others influence components of serum cholesterol. In some cases the effects of the genes are a function of age, sex, or some life style factor such as diet.
We have genotyped each family member for nearly 400 anonymous markers distributed throughout the genome and have performed analyses of linkage and association to detect and localize specific genes that lead to increased risk of heart disease, diabetes, and obesity. So far we have localized genes that influence serum leptin levels, fat mass, insulin, 2 hour glucose, the insulin-glucose ratio, body mass index, VCAM-1, P-selectin, and several lipoprotein measures including LDL-3, HDL cholesterol, HDL2a unesterified cholesterol, and measures of median HDL particle size. We have begun efforts to identify some of these genes. We hope that ultimately we will be able to identify people who, on the basis of the genes they carry, will benefit the most from specific therapies or lifestyle changes.
San Antonio Family Heart Study
Southwest Foundation for Biomedical Research
John Blangero, Program Director
University of Maryland School of Medicine
Baylor College of Medicine
Xing Li Wang
University of Texas Health Science Center at San Antonio
Larry Atwood, Boston University School of Medicine
Daniel O'Leary, New England Medical Center
Paul Samollow, Texas A&M University