Variation in USF1 shows haplotype effects, gene:gene and gene:environment associations with glucose and lipid parameters in the European Atherosclerosis Research Study II

被引:72
作者
Putt, W
Palmen, J
Tahri-Daizadeh, N
Flavell, DM
Humphries, SE
Talmud, PJ
机构
[1] UCL Royal Free & Univ Coll Med Sch, Dept Med, British Heart Fdn Labs, Div Cardiovasc Genet, London WC1E 6JF, England
[2] Univ Paris 06, INSERM, U525, F-75013 Paris, France
关键词
D O I
10.1093/hmg/ddh168
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Upstream stimulatory factor 1 (USF 1), is a transcription factor controlling expression of several genes involved in lipid and glucose homeostasis and co-localizes with familial combined hyperlipidemia (FCHL) and type 2 diabetes on chromosome 1q22-23. We sequenced USF1 in 24 UK FCHL probands, but found no rare or common cSNPs. Three common intronic single nucleotide ploymorphisms (SNP), 306A>G, 475C>T and 1748C>T, were identified and their association was examined with fasting and postprandial lipids and after an oral glucose tolerance test (OGTT) in the European Atherosclerosis Research Study II offspring study. There were no significant differences in allelic frequencies of the SNPs between cases and controls. Individually none of the SNPs showed significant associations with any parameter. In haplotype analysis, compared with other haplotypes, 475C/1748T showed significantly higher and 475T/1748T showed lower peak glucose (P=0.004 and 0.07, respectively) during the OGTT. There was significant case-control heterogeneity in the interaction of genotype with body mass index, on fasting low density lipoprotein with 306A>G and 1748C>T, and on borderline significance with fasting glucose with 475C>T (P=0.002, 0.0007 and 0.015, respectively). Furthermore, 475C>T showed interaction with both HSL-60C>G (case-control heterogeneity P=0.0002) on AUC TG and APOC3 -482C>T on plasma apoE levels (P=0.0012). Thus, in these healthy young men, variation in USF1 was the influencing feature of both glucose and lipid homeostasis showing case-control heterogeneity.
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页码:1587 / 1597
页数:11
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