Both inherited susceptibility and environmental exposure determine the low-density lipoprotein-subfraction pattern distribution in healthy Dutch families

Journal Article · Mon Nov 30 23:00:00 EST 1992 · American Journal of Human Genetics; (United States)

OSTI ID:7063473

Graaf, J de; Swinkels, D W; Haan, A F.J. de; Demacker, P N.M.; Stalenhoef, A F.H. ^[1]

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1. University Hospital, Nijmegen (Netherlands)

A lipoprotein profile characterized by a predominance of small, dense, low-density lipoprotein (LDL) particles has been associated with an increased risk of atherosclerosis. To investigate whether genetic factors are involved in determining this heavy LDL subfraction pattern, this study was undertaken with the aim of resolving the effects that major genes, multifactorial heritability, and environmental exposures have on the LDL subfraction pattern. In a random sample of 19 healthy Dutch families including 162 individuals, the distribution of the LDL subfraction pattern was determined by density gradient ultracentrifugation. For each subject a specific LDL subfraction profile was observed, characterized by the relative contribution of the three major LDL subfractions - LDL1 (d = 1.030-1.033 g/ml), LDL2 (d = 1.033-1.040 g/ml), and LDL3 (d = 1.040-1.045 g/ml) - to total LDL. A continuous variable, parameter K, was defined to characterize each individual LDL subfraction pattern. Complex segregation analysis of this quantitative trait, under a model which includes a major locus, polygenes, and both common and random environment, was applied to analyze the distribution of the LDL subfraction pattern in these families. The results indicate that the LDL subfraction pattern, described by parameter K, is controlled by a major autosomal, highly penetrant, recessive allele with a population frequency of .19 and an additional multifactorial inheritance component. The results indicate that genetic influences as well as environmental exposure, sex, age and hormonal status in women are important in determining the distribution of the LDL subfraction patterns in this population and that these influences may contribute to the explanation of familial clustering of coronary heart disease. 40 refs., 3 figs., 8 tabs.

• OSTI ID: 7063473
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 51:6; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
AGE DEPENDENCE
ANIMALS
ARTERIOSCLEROSIS
BODY
CARDIOVASCULAR DISEASES
CARDIOVASCULAR SYSTEM
CENTRIFUGATION
DENSITY
DISEASES
DISTRIBUTION
ENVIRONMENT
ENVIRONMENTAL EXPOSURE
FEMALES
GENES
HEART
HORMONES
HUMAN POPULATIONS
LIPIDS
LIPOPROTEINS
MAMMALS
MAN
ORGANIC COMPOUNDS
ORGANS
PHYSICAL PROPERTIES
POPULATIONS
PRIMATES
PROTEINS
SEGREGATION
SEPARATION PROCESSES
SEX
ULTRACENTRIFUGATION
VASCULAR DISEASES
VERTEBRATES
WOMEN