title: Variability of plasma apolipoprotein (apo) A-II levels associated with an apo A-II gene polymorphism in monozygotic twin pairs.
abstract: A dimorphic MspI RFLP (alleles M1 and M2) in an Alu unit 528 base pairs downstream from the apolipoprotein A-II gene on chromosome 1 was investigated for associations with dyslipoproteinaemia or coronary atherosclerosis. No significant differences were observed between the allele frequencies in healthy random controls (M2 = 0.850, n = 70) and patients with primary hypertriglyceridaemia (M2 = 0.846, n = 52) or severe coronary atherosclerosis (M2 = 0.819, n = 47). The apolipoprotein A-II gene may also contribute to the regulation of plasma levels or composition of HDL in response to environmental changes. To study the effect upon apolipoprotein A-II variability, 42 monozygotic twin pairs were genotyped for the MspI RFLP. Pairs with the genotype M2M2 (n = 28) had significantly smaller within-pair differences in plasma apolipoprotein A-II levels (2.2 vs 5.8 mg/dl, P < 0.02; Mann-Whitney) than those with other genotypes (n = 14). The M2 allele may be in linkage disequilibrium with a functional mutation that restricts the variability of plasma apolipoprotein A-II in response to environmental conditions. This provides a new example of a 'variability' gene, one of an important group of loci which may alter responses to hypolipidaemic therapy and cardiovascular risk.
authors.affiliation: Department of Human Genetics and Metabolism, St. Bartholomew's Hospital, London, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Thorn
authors.forename: J
authors.initials: J
authors.lastname: Stocks
authors.forename: D
authors.initials: D
authors.lastname: Reichl
authors.forename: J C
authors.initials: JC
authors.lastname: Alcolado
authors.forename: J C
authors.initials: JC
authors.lastname: Chamberlain
authors.forename: D
authors.initials: D
authors.lastname: Galton
mesh_terms: D000328:Adult; D016633:Apolipoprotein A-II / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics; D004277:DNA, Single-Stranded; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D014430:Twins, Monozygotic / Q000235:genetics*
chemical_list: D016633:Apolipoprotein A-II; D004277:DNA, Single-Stranded; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific