We addressed the question: Is there evidence that allelic variation in
a single unmeasured gene that
has a large effect on maximal activity of erythrocyte sodium-lithium
countertransport (Na-Li CNT)
also has pleiotropic effects on variation in plasma triglyceride levels? Complex
segregation analysis
models that included plasma triglyceride levels as a covariate were
considered as explanations for
interindividual variation in Na-Li CNT. A sample of 711 healthy adults from
254 pedigrees enrolled
in the Rochester Family Heart Study was selected for this study. The majority
of the pedigrees
supported the hypothesis that variations in a single unmeasured non-transmitted
environmental
factor have large effects on the Na-Li CNT distribution. Only gender-specific
first-order covariate
parameters were necessary in the complex segregation models suggesting that
the form of the
relationship between Na-Li CNT and plasma triglyceride level was not influenced
by variation in the
inferred environmental factor with large effects. Stratification of the sample
by this inferred
environmental factor resulted in three classes of individuals with significant
differences in the
distributions of coronary heart disease risk factor traits, as well as
interindividual variation in both
Na-Li CNT and plasma triglyceride levels. These results, along with other
observations from the
Rochester Family Heart Study sample, emphasize the complex and multifactorial
nature of the
causes of interindividual variation in Na-Li CNT. Our study further suggests
that new research
strategies are needed for studying the relationships between genetic and
environmental variation
and variation in quantitative traits such as Na-Li CNT that have been identified
as risk factors for hypertension.