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The involvement of upstream stimulatory factor 1 in Dutch patients with familial combined hyperlipidemias⃞ Published, JLR Papers in Press, October 25, 2006.

Recently, the upstream stimulatory factor 1 gene (USF1) was proposed as a candidate gene for familial combined hyperlipidemia (FCH). In this study, we examined the previously identified risk haplotype of USF1 with respect to FCH and its related phenotypes in 36 Dutch FCH families. The diagnosis of FCH was based on both the traditional diagnostic criteria and a nomogram. The two polymorphisms, USF1s1 and USF1s2, were in complete linkage disequilibrium. No association was found for the individual single nucleotide polymorphisms (SNPs) with FCH defined by the nomogram (USF1s1, P = 0.53; USF1s2, P = 0.53), whereas suggestive associations were found when using the traditional diagnostic criteria for FCH (USF1s1, P = 0.08; USF1s2, P = 0.07). USF1 was associated with total cholesterol (USF1s1, P = 0.05; USF1s2, P = 0.04) and apolipoprotein B (USF1s1, P = 0.06; USF1s2, P = 0.04). Small dense LDL showed a suggestive association (USF1s1, P = 0.10; USF1s2, P = 0.09). The results from the haplotype analyses supported the results obtained for the individual SNPs. In conclusion, the previously identified risk haplotype of USF1 showed a suggestive association with FCH and contributed to the related lipid traits in our Dutch FCH families.