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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1997-6-12
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pubmed:abstractText |
Familial combined hyperlipidemia (FCHL) is characterized by different lipid phenotypes (IIa, IIb, IV) and elevated apolipoprotein B (apo B) levels in affected family members. Despite intensive research, the genes involved in the expression of this complex disorder have not been identified, probably because of problems associated with phenotype definition, unknown mode of inheritance, and most probably genetic heterogeneity. To explore the genetics of FCHL in the genetically homogeneous Finnish population, we collected 14 well-documented Finnish pedigrees with premature coronary heart disease and FCHL-like dyslipidemia. The lipolytic enzymes lipoprotein lipase (LPL), hepatic lipase (HL), and hormone-sensitive lipase (HSL) were selected as initial candidate genes because of their central roles in apo B and triglyceride metabolism. On the basis of the pedigree structures, a dominant mode of inheritance was adopted for linkage analyses, and serum total cholesterol and/or triglyceride levels exceeding the 90th percentile level were set as diagnostic criteria (criterion 1). In pairwise linkage analyses with intragenic markers, no evidence for linkage was found. Instead, the significantly negative LOD scores suggested exclusion of all three loci for single major gene effect. LOD scores were -14.63, -5.03, and -5.70 for the three LPL polymorphisms (theta=0.00); -9.40, -6.30, and -4.74 for the three HL polymorphisms (theta=0.00); and -15.29 for the HSL polymorphism (theta=0.00). The results were very similar when apo B levels over the 90th percentile were used as criteria for affected status (criterion 2). Also, when linkage calculations were carried out using an intermediate or recessive mode of inheritance, the results of pairwise linkage analysis remained negative. Furthermore, when haplotypes were constructed from multiple polymorphisms of the LPL and HL genes, no segregation with the FCHL phenotype could be observed in the 14 Finnish families. Data obtained by the affected sib-pair method supported these findings, suggesting that the LPL, HL, or HSL genes do not represent major loci influencing the expression of the FCHL phenotype.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1079-5642
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pubmed:author |
pubmed-author:AntikainenMM,
pubmed-author:EhnholmCC,
pubmed-author:EhnholmSS,
pubmed-author:LahdenkariA TAT,
pubmed-author:Murtomäki-RepoSS,
pubmed-author:NuotioII,
pubmed-author:PajukantaPP,
pubmed-author:PeltonenLL,
pubmed-author:PerolaMM,
pubmed-author:PorkkaK VKV,
pubmed-author:SuurinkeroinenLL,
pubmed-author:SyvänenA CAC,
pubmed-author:TaskinenM RMR,
pubmed-author:ViikariJ SJS
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pubmed:issnType |
Print
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
841-50
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:9157946-Adult,
pubmed-meshheading:9157946-Codon,
pubmed-meshheading:9157946-Female,
pubmed-meshheading:9157946-Finland,
pubmed-meshheading:9157946-Genetic Linkage,
pubmed-meshheading:9157946-Humans,
pubmed-meshheading:9157946-Hyperlipidemia, Familial Combined,
pubmed-meshheading:9157946-Lipase,
pubmed-meshheading:9157946-Lipolysis,
pubmed-meshheading:9157946-Lipoprotein Lipase,
pubmed-meshheading:9157946-Liver,
pubmed-meshheading:9157946-Lod Score,
pubmed-meshheading:9157946-Male,
pubmed-meshheading:9157946-Middle Aged,
pubmed-meshheading:9157946-Pedigree,
pubmed-meshheading:9157946-Polymorphism, Genetic,
pubmed-meshheading:9157946-Prospective Studies,
pubmed-meshheading:9157946-Repetitive Sequences, Nucleic Acid,
pubmed-meshheading:9157946-Sterol Esterase
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pubmed:year |
1997
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pubmed:articleTitle |
No evidence of linkage between familial combined hyperlipidemia and genes encoding lipolytic enzymes in Finnish families.
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pubmed:affiliation |
National Public Health Institute, Department of Human Molecular Genetics, Helsinki, Finland. paivi.pajukanta@ktl.fi
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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