Genetics of dizygotic twinning: A feasibility study for a biobank

To locate the genes that make a substantial contribution to variation in natural dizygotic twinning in humans, large-scale studies are needed. New studies should not stop at DNA genotyping, but collect material that allow gene-expression analysis, transcriptomics, proteomics and endocrinology. In this article we describe a pilot study to examine...

ApoE polymorphism accounts for only part of the genetic variation in quantitative ApoE levels

ApoE levels and chromosome 19 ApoE polymorphisms were measured in a sample of 156 Dutch families. Each pedigree consisted of parents aged 35-65 years and their twin offspring aged 14-21 years. A significant effect of the chromosome 19 apoE locus on quantitative plasma levels of apolipoprotein E was observed. The ApoE polymorphism explained 16%...

Severe hyperlipidemia in apolipoprotein E2 homozygotes due to a combined effect of hyperinsulinemia and an SstI polymorphism

More than 90% of patients with type III hyperlipoproteinemia are homozygous carriers of the apolipoprotein (apo) E*2 allele. The great majority of these apoE2(Arg158→Cys) homozygotes in the general population, however, are normolipidemic. Apparently, expression of the hyperlipidemic state requires additional genetic and/or environmental factors,...

Defective collagen crosslinking in bone, but not in ligament or cartilage, in bruck syndrome: Indications for a bone-specific telopeptide lysyl hydroxylase on chromosome 17

Bruck syndrome is characterized by the presence of osteoporosis, joint contractures, fragile bones, and short stature. We report that lysine residues within the telopeptides of collagen type I in bone are underhydroxylated, leading to aberrant crosslinking, but that the lysine residues in the triple helix are normally modified. In contrast to...

Gender-related association between the -93T →Gg/D9N haplotype of the lipoprotein lipase gene and elevated lipid levels in familial combined hyperlipidemia

Familial combined hyperlipidemia (FCHL) is a frequent cause of premature coronary artery disease. Affected family members are characterized by different combinations of elevated cholesterol and/or triglyceride levels. A reduction in lipoprotein lipase (LPL) activity has been observed in a subgroup of FCHL patients. Recently, we have demonstrated...

The lipoprotein lipase (Asn291 → Ser) mutation is associated with elevated lipid levels in families with familial combined hyperlipidaemia

Familial combined hyperlipidaemia (FCHL) is one of the major genetic causes of coronary heart disease (CHD) and is characterised by elevated levels of plasma cholesterol and/or triglycerides in individuals within a single family. Decreased lipoprotein lipase (LPL) activity has been found in some cases of FCHL. A recent study revealed a common...

An amino acid polymorphism in histidine-rich glycoprotein (HRG) explains 59% of the variance in plasma HRG levels

A pedigree-based maximum likelihood method developed by Lange et al. (12) was used to study the contribution of a newly defined di-allelic polymorphism in histidine-rich glycoprotein (HRG) to the plasma levels of HRG. In four families (n = 99) and 20 volunteers we found a heritability of 70%, an age effect of 3% and an effect of individual...

Identification and genetic analysis of a common molecular variant of histidine-rich glycoprotein with a difference of 2KD in apparent molecular weight

Two forms of histidine-rich glycoprotein (HRG) were detected on SDS-PAGE by silver staining and immunoblotting after isolation of the protein from pooled plasma using immune-affinity chromatography followed by chromatography with heparin-Sepharose. Both forms were single-chain molecules and the apparent molecular weights of form 1 and form 2...

A specific allele of the histidine-rich glycoprotein (HRG) locus is linked with elevated plasma levels of HRG in a Dutch family with thrombosis

Recent studies describe families with both elevated plasma HRG levels and thrombosis. In order to study the possibility that allelic variants of the HRG locus are associated with differences in HRG level, we studied linkage between HRG levels and a dinucleotide repeat polymorphism in a Dutch family which was selected on the presence of both...

An acceptor splice site mutation in intron 16 of the low density lipoprotein receptor gene leads to an elongated, internalization defective receptor

In this report, we describe the characterization of a mutation in the low density lipoprotein (LDL) receptor gene of a true homozygous familial hypercholesterolemic (FH) patient. The combined use of denaturing gradient gel electrophoresis (DGGE) and DNA sequence analysis revealed a unique A to G transition in the penultimate 3'-nucleotide of...

Familial dysbetalipoproteinemia associated with apolipoprotein E3-Leiden in an extended multigeneration pedigree

By the careful screening of familial dysbetalipoproteinemic (FD) patients, five probands showing heterozygosity for the APOE*3-Leiden allele were found. Genealogical studies revealed that these probands share common ancestry in the 17th century. In a group of 128 family members, spanning three generations, 37 additional heterozygous APOE*3...

Elevated plasminogen activator inhibitor (PAI), a cause of thrombophilia? A study in 203 patients with familial or sporadic venous thrombophilia

Two hundred and three patients with venous thrombophilia were investigated in order to find out whether an elevated plasma concentration of plasminogen activator inhibitor (PAI) could be a cause of their tendency to thrombosis. The patients were studied in an asymptomatic period about 3 months after their last thromboembolic episode. PAI...

a2-Antiplasmin Enschede: Dysfunctional alpha 2-antiplasmin molecule associated with an autosomal recessive hemorrhagic disorder

??2-Antiplasmin (??2-AP) is a major fibrinolysis inhibitor, whose complete, congenital absence has been found to be associated with a distinct hemorrhagic diathesis. We studied a 15-yr-old male with a hemorrhagic diathesis after trauma from early childhood on. This bleeding tendency was associated with a minimal ??2-AP level recorded...

A familial hemorrhagic diathesis in a Dutch family: An inherited deficiency of ??2-antiplasmin

This study concerns a case of congenital homozygous deficiency in ??2-antiplasmin associated with a severe hemorrhagic diathesis. Heterozygous family members also show a mild bleeding tendency. The propositus is a 17-yr-old male born of white parents and showing a severe hemorrhagic diathesis characterized by spontaneous bleeding in the joints...