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Sources of variability in genetic association studies: insights from the analysis of hepatic lipase (LIPC).
Hum Mutat. 2002 May; 19(5):536-42.HM

Abstract

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).

Authors+Show Affiliations

Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11968086

Citation

Shohet, Ralph V., et al. "Sources of Variability in Genetic Association Studies: Insights From the Analysis of Hepatic Lipase (LIPC)." Human Mutation, vol. 19, no. 5, 2002, pp. 536-42.
Shohet RV, Vega GL, Bersot TP, et al. Sources of variability in genetic association studies: insights from the analysis of hepatic lipase (LIPC). Hum Mutat. 2002;19(5):536-42.
Shohet, R. V., Vega, G. L., Bersot, T. P., Mahley, R. W., Grundy, S. M., Guerra, R., & Cohen, J. C. (2002). Sources of variability in genetic association studies: insights from the analysis of hepatic lipase (LIPC). Human Mutation, 19(5), 536-42.
Shohet RV, et al. Sources of Variability in Genetic Association Studies: Insights From the Analysis of Hepatic Lipase (LIPC). Hum Mutat. 2002;19(5):536-42. PubMed PMID: 11968086.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sources of variability in genetic association studies: insights from the analysis of hepatic lipase (LIPC). AU - Shohet,Ralph V, AU - Vega,Gloria L, AU - Bersot,Thomas P, AU - Mahley,Robert W, AU - Grundy,Scott M, AU - Guerra,Rudy, AU - Cohen,Jonathan C, PY - 2002/4/23/pubmed PY - 2002/6/28/medline PY - 2002/4/23/entrez SP - 536 EP - 42 JF - Human mutation JO - Hum Mutat VL - 19 IS - 5 N2 - 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). SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/11968086/Sources_of_variability_in_genetic_association_studies:_insights_from_the_analysis_of_hepatic_lipase__LIPC__ L2 - https://doi.org/10.1002/humu.10079 DB - PRIME DP - Unbound Medicine ER -