Effects of the apolipoprotein E polymorphism on levels of lipids, lipoproteins, and apolipoproteins among Mexican-Americans in Starr County, Texas.

Abstract

Genetic variability has been implicated as a significant contributor to the variation in levels of lipids, lipoproteins, and apolipoproteins (apos) through a variety of direct and indirect investigations. Among the direct investigations, apo E has been shown to be polymorphic and to explain a small but statistically significant proportion of the variability in cholesterol. The apo E polymorphism was typed in 964 randomly selected Mexican-Americans from StanCounty, Tex., and its effects determined on levels of cholesterol, triglycerides, total high density lipoprotein (HDL) cholesterol, subtractions (HDL? and HDL,), at-and ^-lipoprotein cholesterol, low density lipoprotein (LDL) cholesterol, and apos A-I, A-II, B, C-II, C-III, and E. Effects are reported for the entire sample and in each of three groups, namely, premenopausal females, postmenopausal women, and males. In the entire sample, significant effects were observed on cholesterol, ^-lipoprotein cholesterol, LDL, apo B, and apo E. There is evidence for significant physiological interaction of the apo E polymorphism effect in females by menopausal status. This is most evident for apo E levels, in which 5.9% of the variability in the entire sample is explained by the apo E polymorphism. In premenopausal females, however, the polymorphism accounts for 27.5% of the variability. In postmenopausal women and males, there is no significant effect It is shown that the apo E polymorphism can be treated as a two-locus, two-allele system. Doing so identifies substitutions in amino acid position 158 as the mediators of most of the observed effects of this polymorphism. [Arteriosclerosis and Thrombosis 1991;ll:362-370) O f the many factors affecting cardiovascular disease risk, cholesterol is one of the best understood. With this understanding has come the technology for measuring cholesterol content in the various lipoprotein particles involved in cholesterol metabolism and the concentrations of many of the associated apolipoproteins (apos). lipid-related measures rather than simple cholesterol levels. Levels of lipids, lipoproteins, and apos vary markedly from individual to individual, and several studies have shown that a significant proportion of this variability is attributable to inferred genetic differences among individuals. 3 -6 Direct studies of genetic variation at loci known to be important in lipid metabolism have revealed how simply inherited variation can contribute to the differences in levels among individuals. The apo E polymorphism 7 ' 8 is among the best studied, and it explains a consistently significant albeit small proportion of the variability in cholesterol levels.9 - 13 The effect has been shown to be primarily on low density lipoprotein (LDL) cholesterol levels and explains approximately 5% or less of the variability observed in the population. 9 -13 Other work has shown that the apo E polymorphism has more substantial effects on concentrations of apo E, explaining as much as 20% or more of the variability in levels of apo E.

Cross-sectional study of risk factors for atherosclerosis in the Azorean population

“…Numerous studies (see among others, Sing and Davignon 1985;Hanis et al 1991;Howard et al 1998) have previously reported associations between variation at the APOE locus and cholesterolemia, which we were able to confirm in the present study. Thus, the e2 allele lowers the concentration of TC and LDL-C levels and the e4 allele raises them.…”

The Relationship Between Risk Factor Levels and Presence of Coronary Artery Calcification is Dependent on Apolipoprotein E Genotype

“…22 These results have raised expectations that the ApoE polymorphism may be useful in identifying asymptomatic individuals who are at higher risk of CAD. However, we also point out that there have also been numerous studies that have found no associations, [23][24][25][26][27][28] or the relative frequency of the ⑀4 allele was actually lower in cases than in control subjects. 48 Other studies have found associations between the frequency of disease (CAD, IHD, and CHD) and the frequency of the ⑀2 allele in addition to an association with the frequency of the ⑀4 allele, 49,50 whereas 1 study only found an association between the presence of carotid artery disease and the presence of the ⑀2 allele.…”

The Distribution of Apolipoprotein E Gene Polymorphism and Apolipoprotein E Levels among Coronary Artery Patients Compared to Controls

“…The gene encoding these three isoforms is located on the human chromosome 19 long arm (19q13.2) and is closely linked with APOC-I/C-II complex [9]. It has been reported that APOE genotype explains 7% of the variation for total cholesterol in healthy white population [10]. In Caucasians, ε4 variant has 15% allele frequency and is associated with early atherosclerosis, mortality, stroke, Alzheimer's disease and myocardial infarction [7,11,12].…”