Linked Life Data

10958645

Source:http://linkedlifedata.com/resource/pubmed/id/10958645

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2000-9-29
pubmed:abstractText
Familial combined hyperlipidemia (FCHL) is the most commonly inherited hyperlipidemia in man, with a frequency of +/-1% in the general population and approximately 10% in myocardial infarction survivors. A genomic scan in 18 Dutch FCHL families resulted in the identification of several loci with evidence for linkage. One of these regions, 1p36.2, contains TNFRSF1B which encodes one of the tumor necrosis factor receptors. An intron 4 polymorphic CA-repeat was used to confirm linkage to FCHL. Linear regression analysis using 79 independent sib pairs showed linkage with a quantitative FCHL discriminant function (P = 0.032), and, borderline, with apolipoprotein B levels (P = 0.064). Furthermore, in a case-control study, association was demonstrated since the overall CA-repeat genotype distribution was significantly different among 40 unrelated FCHL patients and 48 unrelated healthy spouse controls (P = 0.029). This difference was due to a significant increase in allele CA271 homozygotes in the FCHL patients (P = 0.019). Mutation analysis of exon 6 in 73 FCHL family members demonstrated the presence of a single nucleotide polymorphism with two alleles, coding for methionine (196M) and arginine (196R). Complete linkage disequilibrium between CA267, CA271 and CA273 and this polymorphism was detected. In 85 hyperlipidemic FCHL subjects, an association was demonstrated between soluble TNFRSF1B plasma concentrations and the CA271-196M haplotype. In conclusion, TNFRSF1B was found to be associated with susceptibility to FCHL. Our data suggest that an as yet unknown disease-associated mutation, linked to alleles 196M and CA271, plays a role in the pathophysiology of FCHL.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2067-74
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:10958645-Adult, pubmed-meshheading:10958645-Alleles, pubmed-meshheading:10958645-Apolipoproteins B, pubmed-meshheading:10958645-Case-Control Studies, pubmed-meshheading:10958645-Chromosomes, Human, Pair 1, pubmed-meshheading:10958645-DNA Mutational Analysis, pubmed-meshheading:10958645-Exons, pubmed-meshheading:10958645-Family Health, pubmed-meshheading:10958645-Female, pubmed-meshheading:10958645-Genetic Linkage, pubmed-meshheading:10958645-Genotype, pubmed-meshheading:10958645-Haplotypes, pubmed-meshheading:10958645-Humans, pubmed-meshheading:10958645-Hyperlipidemia, Familial Combined, pubmed-meshheading:10958645-Introns, pubmed-meshheading:10958645-Linear Models, pubmed-meshheading:10958645-Linkage Disequilibrium, pubmed-meshheading:10958645-Male, pubmed-meshheading:10958645-Middle Aged, pubmed-meshheading:10958645-Phenotype, pubmed-meshheading:10958645-Polymorphism, Single Nucleotide, pubmed-meshheading:10958645-Receptors, Tumor Necrosis Factor, pubmed-meshheading:10958645-Receptors, Tumor Necrosis Factor, Type II, pubmed-meshheading:10958645-Tumor Necrosis Factor-alpha
pubmed:year
2000
pubmed:articleTitle
Identification of TNFRSF1B as a novel modifier gene in familial combined hyperlipidemia.
pubmed:affiliation
Laboratory of Molecular Metabolism and Endocrinology, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Academic Hospital, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands. j.guerts@intmed.unimaas.nl
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't