Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-5-23
pubmed:abstractText
Genetic association studies have been widely used to identify loci that influence plasma lipoprotein concentrations, but few of the associations reported have proved consistently reproducible across different study populations. This lack of consistency is a widely recognized limitation of association studies, and is often ascribed to inadequate statistical power, population substructure, and population-specific linkage disequilibrium. However, few studies have assessed the causes of variability underlying a given genotype-phenotype association. We have examined two possible sources of variability in the association between the -514 polymorphism in hepatic lipase (LIPC) and plasma HDL-C concentrations. First, we compared the association between this polymorphism and hepatic lipase activity in four populations. A single copy of the -514C allele was associated with a 10 mmol.hr(-1).l(-1) increase in hepatic lipase activity in white American and Turkish men but only approximately 5 mmol.hr(-1).l(-1) in Chinese and African-American men. Second, we tested the effects of a stanozolol-induced increase in hepatic lipase activity on plasma HDL-C concentrations in men with normal (< 150mg/dl) or elevated (150-300mg/dl) levels of plasma triglyceride. The increase in hepatic lipase activity was similar in the two groups, but the resulting decline in HDL-C levels was significantly greater in normolipidemic men. These data suggest that the effect of a polymorphism on gene expression can vary among individuals, and that the resulting phenotype may be further modified by interactions with other factors. Three novel LIPC polymorphisms were identified in the study (-1596insC, -2740A>G, and -2880G>C).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1098-1004
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
536-42
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11968086-Adult, pubmed-meshheading:11968086-African Continental Ancestry Group, pubmed-meshheading:11968086-Alleles, pubmed-meshheading:11968086-Anabolic Agents, pubmed-meshheading:11968086-Asian Continental Ancestry Group, pubmed-meshheading:11968086-Cholesterol, HDL, pubmed-meshheading:11968086-Ethnic Groups, pubmed-meshheading:11968086-European Continental Ancestry Group, pubmed-meshheading:11968086-Gene Frequency, pubmed-meshheading:11968086-Genetic Variation, pubmed-meshheading:11968086-Genotype, pubmed-meshheading:11968086-Humans, pubmed-meshheading:11968086-Linkage Disequilibrium, pubmed-meshheading:11968086-Lipase, pubmed-meshheading:11968086-Liver, pubmed-meshheading:11968086-Male, pubmed-meshheading:11968086-Phenotype, pubmed-meshheading:11968086-Polymorphism, Genetic, pubmed-meshheading:11968086-Stanozolol, pubmed-meshheading:11968086-United States
pubmed:year
2002
pubmed:articleTitle
Sources of variability in genetic association studies: insights from the analysis of hepatic lipase (LIPC).
pubmed:affiliation
Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Multicenter Study