Variation at the apolipoprotein (apo) AI-CIII-AIV gene cluster and apo B gene loci is associated with lipoprotein and apolipoprotein levels in Italian children.
We have used RFLPs of the apolipoprotein (apo) B gene and apo AI-CIII-AIV gene cluster to estimate the genetic contribution of variation at these loci to the variability of plasmid lipid, lipoprotein, and apolipoprotein levels in 209 children from Sezze in central Italy. The sample was randomly divided into group I (107 children) and group II (102 children). Four site polymorphisms (PvuII, XbaI, MspI, and EcoRI) of the apo B gene and five site polymorphisms (XmnI, PstI, SstI, PvuII-CIII, and PvuII-AIV) of the apo AI-CIII-AIV gene cluster were examined in group I children. After adjustment for gender, age, and body-mass index, polymorphisms at both gene loci (PvuII-B, PvuII-CIII, and PvuII-AIV) were associated with significant effects on the levels of plasma apo AI, apo B, or high-density lipoprotein-cholesterol. RFLPs that showed significant effects in group I were genotyped in group II. All three polymorphisms were associated with similar effects on apolipoprotein levels, though for all RFLPs the magnitude of the effects was smaller in the group II children and only statistically significant for the effect of the PvuII-B genotype on apo AI levels. In the total sample of 209 children 7.4% of the sample variance in apo AI levels was explained by variation associated with the apo B PvuII-B RFLP. In addition, the PvuII-B RFLP was associated with significant effects on plasma apo B levels and explained 5.7% of the sample variance. The PvuII-CIII and PvuII-AIV polymorphisms were both associated with differences in apo AI levels, explaining 3.7%-5.7% of the sample variance. Taken together, the three PvuII polymorphisms explained 17.7% of the phenotypic variance in apo AI levels. There was significant evidence for an effect of nonlinearity of the PvuII-CIII genotypes on apo AI levels, with the individuals heterozygous for the polymorphism having the highest apo AI levels. No evidence of interaction between genotype and gender, age, and body-mass index was shown by covariance analysis. The molecular explanation of this effect is unclear. Our data show that variation at both the apo AI-CIII-AIV and apo B loci are associated with lipoprotein and apolipoprotein levels in this sample of Italian children.
Xu
C F
CF
Charing Cross Sunley Research Centre, Hammersmith, London, England.
Nanjee
M N
MN
Savill
J
J
Talmud
P J
PJ
Angelico
F
F
Del Ben
M
M
Antonini
R
R
Mazzarella
B
B
Miller
N
N
Humphries
S E
SE
D000483:Alleles; D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics*; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics*; D001056:Apolipoproteins C / Q000235:genetics*; D002648:Child; D005260:Female; D005796:Genes; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007558:Italy; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D005810:Multigene Family; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D015183:Restriction Mapping
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D008075:Lipoproteins, HDL; C022205:apolipoprotein A-IV