ABCG5/G8 polymorphisms and markers of cholesterol metabolism: systematic review and meta-analysis |
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Authors: | Lily Jakulj Maud N Vissers Michael W T Tanck Barbara A Hutten Frans Stellaard John J P Kastelein Geesje M Dallinga-Thie |
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Institution: | 1. Departments of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;2. Departments of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;4. Departments of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;7. Center for Liver, Digestive and Metabolic Diseases, University Hospital Groningen, Groningen, The Netherlands |
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Abstract: | Genetic variation at the ABCG5/G8 locus has been associated with markers of cholesterol homeostasis. As data originate from small-scale studies, we performed a meta-analysis to study these associations in a large dataset. We first investigated associations between five common ABCG5/G8 polymorphisms (p.Q604E, p.D19H, p.Y54C, p.T400K, and p.A632V) and plasma sterol levels in 245 hypercholesterolaemic individuals. No significant associations were found. Subsequently, our data were pooled into a meta-analysis that comprised 3,364 subjects from 16 studies (weighted mean age, 46.7 ± 10.5 years; BMI, 23.9 ± 3.5 kg/m2). Presence of the minor 632V allele correlated with reduced LDL-C concentrations (n = 367) compared with homozygosity for the 632A variant n = 614; −0.11 mmol/l (95% CI, range: −0.20 to −0.02 mmol/l); P = 0.01]. The remaining polymorphisms were not associated with plasma lipid levels. Carriers of the 19H allele exhibited lower campesterol/TC (n = 83; P < 0.001), sitosterol/TC (P < 0.00001), and cholestanol/TC (P < 0.00001), and increased lathosterol/TC ratios (P = 0.001) compared with homozygous 19D allele carriers (n = 591). The ABCG8 632V variant was associated with a clinically irrelevant LDL-C reduction, whereas the 19H allele correlated with decreased cholesterol absorption and increased synthesis without affecting the lipid profile. Hence, associations between frequently studied missense ABCG5/G8 polymorphisms and markers of cholesterol homeostasis are modest at best. |
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Keywords: | polymorphism LDL-cholesterol plant sterol |
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