title: Cladistic analysis of human apolipoprotein a4 polymorphisms in relation to quantitative plasma lipid risk factors of coronary heart disease.
abstract: Genetic variation in several genes involved in lipid metabolism is known to affect population variation in quantitative lipid risk factor profiles for coronary heart disease (CHD). The apolipoprotein A-IV gene (APOA4) is one such candidate gene. We genotyped five polymorphisms in the APOA4 gene (codon 127, codon 130, codon347, codon 360 and 3' VNTR) and investigated their impact on plasma lipid trait levels in three populations comprising 604 U.S. non-Hispanic Whites (NHWs), 408 U.S. Hispanics and 708 Nigerian Blacks. Cladistic analysis was carried out to identify 5-site haplotypes that were associated with significant phenotypic differences in each population. The distribution of APOA4 genotypes was significantly different between ethnic groups. The Africans were monomorphic for two of the five sites (codons 130 and 360), but possess a unique 12 bp insertion that was not observed in NHWs and Hispanics. Due to linkage disequilibrium between the sites, only 6 haplotypes were observed in NHWs and Hispanics, and 4 in Africans. Several gender-and ethnic-specific associations between genotypes and plasma lipid traits were observed when single sites were used. Several haplotypes were identified by cladistic analysis that may carry functional mutations that affect plasma lipid trait levels.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA 15261, USA.
authors.forename: G Q
authors.initials: GQ
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: DiPietro
authors.forename: K
authors.initials: K
authors.lastname: Roeder
authors.forename: C-K
authors.initials: CK
authors.lastname: Heng
authors.forename: C H
authors.initials: CH
authors.lastname: Bunker
authors.forename: R F
authors.initials: RF
authors.lastname: Hamman
authors.forename: M I
authors.initials: MI
authors.lastname: Kamboh
mesh_terms: D000328:Adult; D000367:Age Factors; D000483:Alleles; D001054:Apolipoproteins A / Q000235:genetics*; D044383:Black People; D003062:Codon; D003327:Coronary Disease / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D015233:Models, Statistical; D010641:Phenotype; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012737:Sex Factors; D044465:White People
chemical_list: D001054:Apolipoproteins A; D003062:Codon; C022205:apolipoprotein A-IV