Effects of apolipoprotein A-I genetic variations on plasma apolipoprotein, serum lipoprotein and glucose levels

被引:28
作者
Larson, IA
Ordovas, JM
Barnard, JR
Hoffmann, MM
Feussner, G
Lamon-Fava, S
Schaefer, EJ
机构
[1] Tufts Univ, Sch Med, New England Med Ctr,Lipid Metab Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA
[2] Heidelberg Univ, Sch Med, Dept Internal Med, Heidelberg, Germany
[3] Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA USA
[4] Univ Freiburg, Dept Clin Chem, Freiburg, Germany
关键词
apolipoprotein A-1; apolipoproteins; haplotype; lipids; lipoproteins; polymorphism;
D O I
10.1034/j.1399-0004.2002.610302.x
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The present authors investigated the individual and combined associations of the apolipoprotein (apo) A-I -75 bp and +83 bp polymorphisms with plasma lipid, lipoprotein and apolipoprotein levels in 734 Caucasian men and women. The frequency of the A allele at position -75 bp (G-->A) was 0.14 in women and 0.17 in men. The frequencies for the rare M2 allele at position +83 bp and/or 84 bp (C-->T and G-->A, respectively) were 0.04 and 0.05 in women and men, respectively. In women, the A allele was associated with significantly higher levels of apo B (P = 0.016), total cholesterol (TC) (P = 0.005), low-density lipoprotein cholesterol (LDL-C) (P = 0.018) and TC:high-densisty lipoprotein (HDL) ratio (P = 0.026) compared to the G/G subjects. In men, no significant associations were detected between the -75 bp polymorphism and any lipid trait examined. The M2 allele for the +83 bp polymorphism was significantly associated in men with higher levels of apo A-I (P = 0.002) and TC (P = 0.046). In women, a significant effect was observed for TC (P = 0.036), with M2+/- subjects having lower levels than M2+/+ subjects. Significant linkage disequilibrium (P = 0.037) between the apo A-I -75 bp and +83 bp polymorphisms was detected. Women carrying both rare alleles (G/A M2+/-) had significantly hi-her TC:HDL ratios (P = 0.031) compared to the other haplotypes. In men, significant differences were observed for apo A-I (P = 0.021) and TC (P = 0.044), with carriers of the G/G M2+/- haplotype having the highest values compared to other genotype combinations. In conclusion, the -75 bp (G/A) polymorphism appears to have a significant effect on levels of apo B, plasma TC and LDL-C in women, while the +83 bp polymorphism seems to affect the apo A-I levels in men, and the plasma cholesterol levels in both genders.
引用
收藏
页码:176 / 184
页数:9
相关论文
共 68 条
[1]  
AKITA H, 1995, HUM GENET, V96, P521
[2]   EFFECTS OF LIFE-STYLE MODIFICATION ON SERUM-LIPIDS [J].
BARNARD, RJ .
ARCHIVES OF INTERNAL MEDICINE, 1991, 151 (07) :1389-1394
[3]  
BARRE DE, 1994, J LIPID RES, V35, P1292
[4]   APOLIPOPROTEIN PROFILE IN HEALTHY-MALES AND ITS RELATION TO MAXIMUM AEROBIC CAPACITY (MAC) [J].
BERG, A ;
FREY, I ;
KEUL, J .
CLINICA CHIMICA ACTA, 1986, 161 (02) :165-171
[5]   Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency [J].
Brooks-Wilson, A ;
Marcil, M ;
Clee, SM ;
Zhang, LH ;
Roomp, K ;
van Dam, M ;
Yu, L ;
Brewer, C ;
Collins, JA ;
Molhuizen, HOF ;
Loubser, O ;
Ouelette, BFF ;
Fichter, K ;
Ashbourne-Excoffon, KJD ;
Sensen, CW ;
Scherer, S ;
Mott, S ;
Denis, M ;
Martindale, D ;
Frohlich, J ;
Morgan, K ;
Koop, B ;
Pimstone, S ;
Kastelein, JJP ;
Genest, J ;
Hayden, MR .
NATURE GENETICS, 1999, 22 (04) :336-345
[6]   Influence of genetic variation at the apo A-I gene locus on lipid levels and response to diet in familial hypercholesterolemia [J].
Carmena-Ramon, RF ;
Ordovas, JM ;
Ascaso, JF ;
Real, J ;
Priego, MA ;
Carmena, R .
ATHEROSCLEROSIS, 1998, 139 (01) :107-113
[7]   LOCALIZATION OF THE STRUCTURAL GENE FOR HUMAN APOLIPOPROTEIN A-I ON THE LONG ARM OF HUMAN CHROMOSOME-11 [J].
CHEUNG, P ;
KAO, FT ;
LAW, ML ;
JONES, C ;
PUCK, TT ;
CHAN, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (02) :508-511
[8]   NUCLEOTIDE-SEQUENCE OF CLONED CDNA OF HUMAN APOLIPOPROTEIN A-I [J].
CHEUNG, P ;
CHAN, L .
NUCLEIC ACIDS RESEARCH, 1983, 11 (11) :3703-3715
[9]  
CIVEIRA F, 1993, CLIN GENET, V44, P307
[10]  
Contois JH, 1996, CLIN CHEM, V42, P515