MULTIPLE GENETIC-DETERMINANTS OF VARIATION OF PLASMA-LIPOPROTEINS IN ALBERTA HUTTERITES

被引:78
作者
HEGELE, RA
BRUNT, JH
CONNELLY, PW
机构
[1] UNIV TORONTO,ST MICHAELS HOSP,DEPT MED,TORONTO,ON M5B 1W8,CANADA
[2] UNIV TORONTO,ST MICHAELS HOSP,DEPT CLIN BIOCHEM,TORONTO,ON M5B 1W8,CANADA
[3] UNIV TORONTO,ST MICHAELS HOSP,DEPT BIOCHEM,TORONTO,ON M5B 1W8,CANADA
[4] UNIV VICTORIA,SCH NURSING,VICTORIA,BC,CANADA
关键词
GENETIC ASSOCIATION STUDY; DNA MARKERS; POLYGENIC TRAITS;
D O I
10.1161/01.ATV.15.7.861
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We hypothesized that variation of nine candidate genes in lipoprotein metabolism would be associated with variation in fasting plasma lipoprotein variables in 718 Alberta Hutterites, a genetic isolate. We measured plasma lipids, lipoproteins, and apolipoproteins and analyzed DNA for genotypes of apolipoprotein (apo) B (APOB), paraoxonase (PON), lipoprotein lipase (LPL), VLDL receptor (VLDLR), apo CIII (APOC3), LDL receptor-related protein (LRP), hepatic lipase (HL), LDL receptor (LDLR), and apo E (APOE). Using a multivariate analysis, we found that (1) genotypes of APOB, PON, LPL, LDLR, and APOE were significantly associated with variation of plasma apo B-related traits; (2) genotypes of PON, LPL, and APOC3 were significantly associated with variation in plasma triglycerides; and (3) genotypes of VLDLR, APOC3, LDLR, and APOE were significantly associated with variation in plasma apo AI and HDL cholesterol. Regression analysis showed that between 3.2% and 7.8% of the total variation in plasma lipoproteins was accounted for by variation in the candidate genes tested. The observations demonstrate a modest but significant genetic component of variation in plasma lipoprotein levels that is due to the candidate genes studied in this normolipemic human genetic isolate.
引用
收藏
页码:861 / 871
页数:11
相关论文
共 26 条
[1]   RAPID TYPING OF APOLIPOPROTEIN-B DNA POLYMORPHISMS BY DNA AMPLIFICATION - ASSOCIATION BETWEEN AG EPITOPES OF HUMAN APOLIPOPROTEIN B-100, A SIGNAL PEPTIDE INSERTION DELETION POLYMORPHISM, AND A 3' FLANKING DNA VARIABLE NUMBER OF TANDEM REPEATS POLYMORPHISM OF THE APOLIPOPROTEIN-B GENE [J].
BOERWINKLE, E ;
LEE, SS ;
BUTLER, R ;
SCHUMAKER, VN ;
CHAN, L .
ATHEROSCLEROSIS, 1990, 81 (03) :225-232
[2]  
BRUNT JH, 1992, CAN J PUBLIC HEALTH, V83, P362
[3]  
CONNELLY PW, 1992, CAN MED ASSOC J, V146, P1977
[4]   AN APOLIPOPROTEIN CIII HAPLOTYPE PROTECTIVE AGAINST HYPERTRIGLYCERIDEMIA IS SPECIFIED BY PROMOTER AND 3' UNTRANSLATED REGION POLYMORPHISMS [J].
DAMMERMAN, M ;
SANDKUIJL, LA ;
HALAAS, JL ;
CHUNG, W ;
BRESLOW, JL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (10) :4562-4566
[5]   APOLIPOPROTEIN-E POLYMORPHISM AND ATHEROSCLEROSIS [J].
DAVIGNON, J ;
GREGG, RE ;
SING, CF .
ARTERIOSCLEROSIS, 1988, 8 (01) :1-21
[6]  
FUJIWARA TM, 1989, AM J HUM GENET, V44, P327
[7]   THE COLLABORATIVE LIPID RESEARCH CLINICS PROGRAM FAMILY STUDY .3. TRANSFORMATIONS AND COVARIATE ADJUSTMENTS OF LIPID AND LIPOPROTEIN LEVELS [J].
GREEN, PP ;
NAMBOODIRI, KK ;
HANNAN, P ;
MARTIN, J ;
OWEN, ARG ;
CHASE, GA ;
KAPLAN, EB ;
WILLIAMS, L ;
ELSTON, RC .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 1984, 119 (06) :959-974
[8]   A POLYMORPHISM OF THE PARAOXONASE GENE ASSOCIATED WITH VARIATION IN PLASMA-LIPOPROTEINS IN A GENETIC ISOLATE [J].
HEGELE, RA ;
BRUNT, JH ;
CONNELLY, PW .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1995, 15 (01) :89-95
[9]   A GENE-GENDER INTERACTION AFFECTING PLASMA-LIPOPROTEINS IN A GENETIC ISOLATE [J].
HEGELE, RA ;
EVANS, AJ ;
TU, LL ;
IP, G ;
BRUNT, JH ;
CONNELLY, PW .
ARTERIOSCLEROSIS AND THROMBOSIS, 1994, 14 (05) :671-678
[10]  
Hegele Robert A., 1992, Human Mutation, V1, P320, DOI 10.1002/humu.1380010410