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Polymorphism in the promoter region of the apolipoprotein AI gene associated with differences in apolipoprotein AI levels: The European Atherosclerosis Research Study

机译:Polymorphism in the promoter region of the apolipoprotein AI gene associated with differences in apolipoprotein AI levels: The European Atherosclerosis Research Study

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AbstractThe effect associated with the substitution of adenine (A) for guanidine (G) in the promoter region of the apolipoprotein AI gene (−75 bp) with plasma apo AI and high‐density lipoprotein (HDL) levels was investigated in the European Atherosclerosis Research Study (EARS). This is a study of healthy offspring (cases) of fathers who had suffered premature myocardial infarction (MI) before age 55 years (n= 565) and age‐ and sex‐matched controls (n= 1,078) from 12 European countries, divided into 5 regions based on geography and language. The frequency of the polymorphism was not significantly different among the regions and the relative frequency of the rareAallele was similar in cases and controls (0.159 vs. 0.142) combining data from all regions. Individuals with one or moreAallele had significantly higher plasma apo AI levels (P<0.05) than individuals homozygous for theGallele. This effect was consistent in all regions. The data were analyzed separately in males and females. In females, those with one or moreAallele had significantly higher apo AI levels (P= 0.05) than individuals homozygous for theGallele, and this raising effect of theAallele was greater in cases than controls for both apo AI (5.23 vs. 1.56) and HDL (4.48 vs. 1.89). In males, theAallele was associated with higher levels of apo AI and HDL, but the effect was much smaller and the differences did not reach statistical significance. In the females, where the effect of theAallele was strongest, the effect on apo AI associated with genotype was evident in non‐smokers, and individuals with one or twoAalleles had 3.6 higher apo AI and 3.14 higher HDL levels than individuals homozygous for theGallele. However, in the female smokers the raising effect of theAallele was greatly reduced (0.56). Thus genetic variation in the promoter region of the apo AI gene is associated with differences in apo AI and HDL levels in healthy individuals throughout Europe, but the effect is modulated by gender, environmental factors such as smoking, and a family hist

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