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New MspI polymorphism at +83 bp of the human apolipoprotein al gene: Association with increased circulating high density lipoprotein cholesterol levels
Author(s) -
Wang X.L.,
Badenhop R.,
Humphrey K.E.,
Wilcken D.E.L.
Publication year - 1996
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/(sici)1098-2272(1996)13:1<1::aid-gepi1>3.0.co;2-d
Subject(s) - apolipoprotein b , polymorphism (computer science) , genetics , lipoprotein , cholesterol , biology , gene , high density lipoprotein , apolipoprotein c2 , medicine , genotype , endocrinology , very low density lipoprotein
We recently showed that loss of a Msp I restriction site in the 5′‐end(intron 1) of the apolipoprotein (apo) AI gene is due to a C to T transition (+83 bp) and/or aG to A transition (+84 bp). Since this region may be relevant to the regulation of apo AI geneexpression and therefore to plasma high density lipoprotein cholesterol (HDL‐C), we exploredthe association between this Msp I polymorphic site and circulating HDL‐C levels in243 healthy Caucasians. There were 143 aged 18–67 years (60 males and 83 females)and 100 aged 6–12 years (58 males and 42 females). We also compared thisassociation with a known Msp I polymorphic site, a G to A transition at −75 bpof the apo AI gene. The rare allele (−) frequency for the polymorphism at +83 bp was4.1% and 22.1% for the polymorphism at −75 bp. Subjects heterozygous for the lossof the Msp I restriction site at +83 bp (genotype: M2+−, n = 20) hadhigher HDL‐C levels than M2++ subjects (mean ± SD: 1.73 ± 0.31 vs. 1.41± 0.39 mmol/l, P < 0.05 for adults; 1.71 ± 0.33 vs. 1.34 ±0.29 mmol/l, P < 0.01 for children). Adults with the G to A substitution at−75 bp also had higher HDL‐C levels (1.56 ± 0.36 mmol/l for AA, 1.53± 0.38 mmol/l for GA, and 1.36 ± 0.38 mmol/l for GG, P < 0.05);this difference was not observed in the children. The Msp I polymorphisms at bothsites were in linkage disequilibrium. Their joint effect on the HDL‐C levels was alsosignificant and individuals with rare alleles (−) at both sites had the highest HDL‐Clevels. In an analysis of variance, the Msp I polymorphism at +83 bp, and at−75 bp and gender independently accounted for 6.5%, 1.7%, and 5.9%, respectively, ofthe variance in circulating HDL‐C levels when age was controlled as a covariate. Weconclude that loss of the Msp I site by the C to T (+83 bp) and/or the G to A (+84 bp)transitions is highly associated with increased HDL‐C levels. The association appears to bemore significant than that of the G to A transition at −75 bp. © 1996 Wiley‐Liss,Inc.