Role of the apolipoprotein A-IV polymorphism at codon 347 in affecting normal plasma lipid and apolipoprotein variation
- Univ. of Pittsburgh, PA (United States); and others
Apolipoprotein A-IV (APOA-IV) is a major component of several lipoprotein particles, and is therefore expected to play an important role in lipid metabolism. Sequence analysis of the APOA-IV coding region has revealed a common nucleotide substitution at codon 347 which converts the commonly present threonine residue (allele A) into serine (allele T). In this investigation, we determined the APOA-IV polymorphism at codon 347 by polymerase chain reaction-based assay in 537 normolipidemic non-Hispanic Whites (NHWs), and 377 normolipidemic Hispanics from the San Luis Valley, Colorado, and examined its effect on quantitative lipid and apolipoprotein traits. The frequency of the less common allele (APOA-IV*T) was significantly lower in Hispanics than in NHWs (0.13 vs. 0.20; P<0.01), most probably due to substantial Amerindian admixture. After adjusting for concomitant variables including age, cigarette smoking, body mass index and premenopausal or postmenopausal status in women, we found significant ethnic and gender-specific effects of the APOA-IV polymorphism on plasma levels of APOA-I (P=0.01) and LP(a) (P=0.03) in NHW women only. There was a clear gene dosage effect on the two quantitative traits: APOA-I levels were lowest in the TT genotype, intermediate in the AT genotype, and highest in the AA genotype; the trend was reversed for LP(a) levels among the three genotypes. The average effect of the APOA-IV*T allele was to lower APOA-I levels by 7.8 mg/dl and to raise LP(a) levels by 2.6 mg/dl. These data suggest that the APO-IV*T allele may be associated with atherogenic apolipoprotein profile in NHW women as lower levels of APOA-I and higher levels of LP(a) are considered to be major risk factors for coronary heart disease.
- OSTI ID:
- 133953
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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