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标题：Heritability and genetic loci of fatty liver in familial combined hyperlipidemia
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作者：Brouwers, Martijn C. G. J. ; Cantor, Rita M. ; Kono, Naoko 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2006
卷号：47
期号：12
页码：2799-2807
DOI：10.1194/jlr.M600312-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：VLDL overproduction, a process that is driven by an excess amountof hepatic fat, is a well-documented feature of familial combinedhyperlipidemia (FCHL). The aims of this study were to investigatewhether fatty liver, measured with ultrasound and as plasmaalanine aminotransferase (ALT) levels, develops against a geneticbackground in FCHL and to identify chromosomal loci that arelinked to these traits. In total, 157 FCHL family members and20 spouses participated in this study. Radiological evidenceof fatty liver was more prevalent not only in FCHL probands(40%) but also in their relatives (35%) compared with spouses(15%) (P < 0.05). Heritability calculations revealed that20–36% of the variability in ALT levels could be attributedto genetic factors. Nonparametric quantitative trait locus (QTL)analysis revealed three significant (P < 0.001) loci witheither the ultrasound or the ALT trait in the male sample: 1q42.3,7p12-21, and 22p13-q11; none was found in the female sampleor the entire group. Of these QTLs, the 7p region was consistentover time, because reanalysis with ALT levels that were determinedduring a visit 5 years earlier yielded similar results. Thisstudy shows that fatty liver is a heritable aspect of FCHL.Replication of particularly the 7p region is awaited. Supplementary key words steatosis • nonalcoholic fatty liver disease • quantitative trait locus • linkage analysis • alanine aminotransferase