title: Linkage disequilibrium of three polymorphic RFLP markers in the apolipoprotein AI-CIII gene cluster on chromosome 11.
abstract: We analysed the allelic and genotypic frequencies of three restriction fragment length polymorphisms in the region of chromosome 11 encoding apolipoprotein AI and CIII genes in a free-living population from South Italy (Calabria). These markers are located at -2500 and -78 bp from the transcription start site of apolipoprotein AI gene (XmnI and MspI, respectively), and in the 3' untranslated region of apolipoprotein CIII gene (SstI). XmnI and SstI label rare alleles (X2 and S2 indicate the presence of the site), whereas the absence of the MspI site (because of a G to A transition) marks the rare allele, M2. Pairwise linkage disequilibrium analysis was determined. Two significant non-random associations were found: a positive disequilibrium between ApoA1/XmnI and ApoA1/MspI markers (P < 0.0001), and a negative disequilibrium between ApoA1/XmnI and ApoC3/SstI markers (P < 0.05). Statistical analysis showed a significant difference in the S2-M2 haplotype frequency between the group of subjects with serum cholesterol levels in the highest decile (P < 0.005) and the group with serum cholesterol levels below the highest decile. The allelic frequency for each locus showed no significant difference between the two groups for all other metabolic parameters, included total cholesterol serum levels. These haplotypes are a more precise measure of genetic variations in the apolipoprotein cluster and their use should allow the mapping of mutations responsible for high serum cholesterol levels.
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgie, Università degli Studi di Reggio Calabria, Catanzaro, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Marasco
authors.forename: F
authors.initials: F
authors.lastname: Melina
authors.forename: E
authors.initials: E
authors.lastname: Mele
authors.forename: B
authors.initials: B
authors.lastname: Quaresima
authors.forename: A
authors.initials: A
authors.lastname: Zingone
authors.forename: E
authors.initials: E
authors.lastname: Focarelli
authors.forename: E
authors.initials: E
authors.lastname: Picciotti
authors.forename: M L
authors.initials: ML
authors.lastname: Martelli
authors.forename: L
authors.initials: L
authors.lastname: Fotino
authors.forename: M F
authors.initials: MF
authors.lastname: Vigna
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016632:Apolipoprotein A-I / Q000235:genetics; D053305:Apolipoprotein C-III; D001053:Apolipoproteins / Q000235:genetics*; D001056:Apolipoproteins C / Q000235:genetics; D001483:Base Sequence; D015139:Blotting, Southern; D016009:Chi-Square Distribution; D002880:Chromosomes, Human, Pair 11; D004247:DNA / Q000032:analysis; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA
chemical_list: D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001053:Apolipoproteins; D001056:Apolipoproteins C; D005819:Genetic Markers; D008055:Lipids; D004247:DNA