Journal of Lipid Research, Vol 35, 1292-1296, Copyright © 1994 by Lipid Research, Inc.

ARTICLES

Genetic analysis of a polymorphism in the human apolipoprotein A-I gene promoter: effect on plasma HDL-cholesterol levels

DE Barre, R Guerra, R Verstraete, Z Wang, SM Grundy and JC Cohen
Center for Human Nutrition, UT Southwestern Medical Center, Dallas 75235-9052.

Previous studies have indicated that a G to A substitution at position - 76 in the gene encoding apolipoprotein A-I (apoA-I) confers increased plasma high density lipoprotein cholesterol (HDL-C). Increased HDL-C may be a direct consequence of the A allele, or may reflect the action of a locus in linkage disequilibrium with the A allele. To elucidate this question, we examined the effect of this polymorphism in a large sample (n = 409) of unrelated Caucasians and their nuclear families (n = 22). To eliminate the confounding effects of hypertriglyceridemia, individuals with triglyceride levels greater than 150 mg/dl were excluded from the study. ApoA-I genotype was determined by polymerase chain reaction (PCR) amplification of genomic DNA and restriction digestion with Msp I. Individuals were grouped by genotype (GG, GA or AA) and mean adjusted HDL levels of the three groups were compared by one-way analysis of variance. Our analysis indicates that HDL-C levels do not vary by genotype, and no gene dosage effect is apparent in men or in women. Analysis of 22 informative Caucasian nuclear families showed no significant difference between individuals with the A allele and their GG siblings. These data suggest that polymorphism at -76 in the apoA-I gene does not directly affect HDL levels. Therefore, the increased HDL-C levels reported in other populations must reflect linkage disequilibrium between the A allele and a putative HDL-raising allele. As we find no evidence for association between the A allele and high HDL levels, this putative allele must occur at a low frequency in the population sampled in this study.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. M Ordovas Genetic interactions with diet influence the risk of cardiovascular disease Am. J. Clinical Nutrition, February 1, 2006; 83(2): 443S - 446S. [Abstract] [Full Text] [PDF]

				M. A Pereira, R. M Weggemans, D. R Jacobs Jr, P. J Hannan, P. L Zock, J. M Ordovas, and M. B Katan Within-person variation in serum lipids: implications for clinical trials Int. J. Epidemiol., June 1, 2004; 33(3): 534 - 541. [Abstract] [Full Text] [PDF]

				K. E. Berge, K. von Bergmann, D. Lutjohann, R. Guerra, S. M. Grundy, H. H. Hobbs, and J. C. Cohen Heritability of plasma noncholesterol sterols and relationship to DNA sequence polymorphism in ABCG5 and ABCG8 J. Lipid Res., March 1, 2002; 43(3): 486 - 494. [Abstract] [Full Text] [PDF]

				J. M Ordovas, D. Corella, L A. Cupples, S. Demissie, A. Kelleher, O. Coltell, P. W. Wilson, E. J Schaefer, and K. Tucker Polyunsaturated fatty acids modulate the effects of the APOA1 G-A polymorphism on HDL-cholesterol concentrations in a sex-specific manner: the Framingham Study Am. J. Clinical Nutrition, January 1, 2002; 75(1): 38 - 46. [Abstract] [Full Text] [PDF]

				A. Matsunaga, J. Sasaki, H. Han, W. Huang, M. Kugi, T. Koga, S. Ichiki, T. Shinkawa, and K. Arakawa Compound Heterozygosity for an Apolipoprotein A1 Gene Promoter Mutation and a Structural Nonsense Mutation With Apolipoprotein A1 Deficiency Arterioscler. Thromb. Vasc. Biol., February 1, 1999; 19(2): 348 - 355. [Abstract] [Full Text] [PDF]

				S. H. Hong, W. H. Park, C. C. Lee, J. H. Song, and J. Q Kim Association between genetic variations of apo AI-CIII-AIV cluster gene and hypertriglyceridemic subjects Clin. Chem., January 1, 1997; 43(1): 13 - 17. [Abstract] [Full Text] [PDF]

				A. Minnich, G. DeLangavant, J. Lavigne, G. Roederer, S. Lussier-Cacan, and J. Davignon G->A Substitution at Position -75 of the Apolipoprotein A-I Gene Promoter : Evidence Against a Direct Effect on HDL Cholesterol Levels Arterioscler. Thromb. Vasc. Biol., October 1, 1995; 15(10): 1740 - 1745. [Abstract] [Full Text]