textThe goal of this project was to study the genetic structure of the metabolic
syndrome. The first objective was to locate chromosomal regions influencing
insulin resistance in Mexican Americans of the San Antonio Family Heart Study
(SAFHS). Two studies were performed to achieve this objective using a genomewide
scan. In the first study using data from the first visit of the SAFHS, we
detected significant linkage evidence on chromosome 8p between marker
D8S1130 and D8S1106 and on chromosome 13q between marker D13S787 and
D13S252. In the second study that used data from the second visit of the SAFHS,
markers D1S1663 on chromosome 1 and D2S436 on chromosome 2 were found to
be linked to insulin sensitivity indices. Candidate genes on detected locations
were proposed. The significant findings in both studies duplicate those of
previous investigations. The second objective of this project was to identify the
genetic locations related to the quantitative traits that constitute the metabolic
syndrome in the same population of Mexican Americans. Principal component
factor analysis (PCFA) was conducted, and significant and suggestive evidence
for linkage of lipid (factor 4) and body size/adiposity (factor 1) were found on
chromosome 4 near marker D4S403 and chromosome 1 near marker D1S1597,
respectively. The third objective of this project was to explore the genetic
pleiotropy between insulin resistance and adiposity, especially visceral obesity
using the baboon as a model. The present study is the first to use omental tissue to
investigate gene pleiotropy between visceral fat and insulin resistance. The results
from the baboon study in this thesis, coupled with research in humans, suggest
that a common set of genes contribute to insulin resistance and obesity in both
species. It is also plausible that those two groups of genes completely overlap
each other. At present, the variance decomposition based, multipoint linkage
analysis is a mathematical model that can provide useful information for
susceptible gene mapping. Future finemapping and the positional candidate gene
approach will be helpful to further our understanding of the genetic structure of
this complex disease.Nutritional Science
