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K Aalto-Setälä

Publications and source records attributed to K Aalto-Setälä.

At least 19 recordsLinked to original sources
PubMed2004

Heat shock protein 60 autoimmunity and early lipid lesions in cholesterol-fed C57BL/6JBom mice during Chlamydia pneumoniae infection.

Chronic Chlamydia pneumoniae infection and autoimmunity to heat shock protein 60 (Hsp60) have both been documented to be associated with atherosclerosis. Herein, we studied the effects of C. pneumoniae infection and a diet with a low-cholesterol supplement on the development of autoantibodies to mouse Hsp60 and early lipid lesions in the aortic valve of C57BL/6JBom mice. In addition, pulmonary infection was investigated. C57BL/6JBom mice were given one to three C. pneumoniae inoculations and fed either a regular diet or a diet enriched with 0.2% cholesterol. Autoantibody responses against mouse Hsp60 developed in both diet groups when the mice were infected with C. pneumoniae and in uninfected mice fed a cholesterol-enriched diet. C. pneumoniae infections increased subendothelial foam cell accumulation in mice on a 0.2% cholesterol-enriched diet (p = 0.022), without apparent hypercholesterolemia. These in vivo data suggest that autoantibodies against mouse Hsp60 develop as a consequence of cholesterol feeding and repeated C. pneumoniae infections. Further, infectious burden increased early lipid lesions in C57BL/6JBom mice fed a cholesterol-enriched diet.

Animals↗
PubMed2001

Chlamydia pneumoniae does not increase atherosclerosis in the aortic root of apolipoprotein E-deficient mice.

In epidemiological studies, an association between cardiovascular disease and Chlamydia pneumoniae (C pneumoniae) infection has been observed. Although C pneumoniae has been shown to be present in atherosclerotic lesions, a causal relationship between C pneumoniae infection and atherosclerosis has not been demonstrated. To study this question, we used 2 strains of apolipoprotein (apo) E-deficient mice. Eight-week-old mice on an FVB background that were maintained on either a low- or a high-fat diet were infected 3 times at 1-week intervals with C pneumoniae, and atherosclerotic lesions were measured in the aortic root at 10 weeks after the primary infection. In each of the diet groups, no difference in the extent of atherosclerosis could be observed between the C pneumoniae-infected and control animals. In further studies, 2 strains of apoE-deficient mice (FVB or C57BL/6J background) were infected 4 times at 3- to 4-week intervals, and the extent of atherosclerosis was analyzed 18 weeks later. The mice were kept on either a low- or a high-fat diet. The high-fat diet increased atherosclerosis, and a difference in atherosclerosis susceptibility between the mouse strains was observed. However, C pneumoniae infection did not influence lesion size in either mouse strain. On the other hand, C pneumoniae could not be demonstrated by polymerase chain reaction in any of the atherosclerotic lesions of the infected animals studied. A small decrease in serum cholesterol and triglyceride levels 3 days after the primary infection occurred, but after that no differences in serum lipid levels compared with those in noninfected animals were evident. In the myocardium of C pneumoniae-infected mice, no inflammatory signs could be observed. We conclude that under the experimental conditions used, C pneumoniae infection does not accelerate atherogenic changes in the aortic root of apoE-deficient mice.

Animals↗
PubMed2001

Familial hypercholesterolaemia in Finland: common, rare and mild mutations of the LDL receptor and their clinical consequences. Finnish FH-group.

Familial hypercholesterolaemia (FH) is an autosomal co-dominantly inherited condition resulting from mutations of the low-density lipoprotein (LDL) receptor which occur in heterozygous form in approximately one in 500 individuals. Clinically, FH is characterized by 2-3-fold elevation of serum LDL cholesterol levels, accelerated development of atherosclerotic vascular disease, and, if untreated, shortened lifespan. The Finnish population, which represents a genetic isolate, offers exceptional possibilities for genetic-epidemiological studies on FH, as a handful of founder gene mutations account for the majority of FH cases in Finland. This review summarizes data from our FH studies carried out since 1985. We wish to emphasize the continuum of genotype-phenotype relationships, the importance of molecular diagnosis, the detection of novel risk factors of vascular disease, and innovations inhibiting cholesterol absorption for the modern treatment of FH.

Age of Onset↗
PubMed2000

Puromycin-induced lipid peroxidation in the cochlea of ApoE knockout mice.

Puromycin-treated apolipoprotein E (ApoE)-deficient mice were used to study lipid peroxidation (LPO) in the cochlea. Puromycin causes accelerated peroxidation of lipids and induces both inner ear and renal lesions in experimental animals presenting with abnormally high serum cholesterol. To prevent LPO, we used probucol, an effective inhibitor of LPO, and, simultaneously, also a lipid-lowering drug. The mice were given a single injection of the aminonucleoside of puromycin (25 mg/100 g). Polyclonal malondialdehyde and 4-hydroxynonenal antibodies were used to localize the LPO products. LPO products were mainly found in the stria vascularis of puromycin-treated mice. No LPO products were observed in the hair cells. LPO product immunoreactivity was clearly diminished in the animal group treated with both puromycin and probucol. In the cochlea of the ApoE-deficient mouse, puromycin affects mainly the stria vascularis due to the accelerated peroxidation of structural lipids. Probucol treatment prevented the formation of LPO products.

Animals↗
PubMed1999

European Lipoprotein Club: report of the 21st Annual Conference, Tutzing, September 28-October 1, 1998.

Molecular biology and genetics were the hallmarks of the conference. Attendees from 20 European countries participated in lively discussions with international speakers. The opening round table session entitled 'Genetic approach to complex diseases' was chaired by Harald Funke. Steve Humphries (London) presented association studies and Harald Funke (Munster) presented multiparameter analyses, as models of genetic epidemiological approaches to atherosclerosis. Gerd Utermann (Innsbruck) showed, through sib pair linkage analysis, how apo (a) gene polymorphism determines plasma levels of Lp(a). Klaus Lindpainter (Basel) described novel genetic strategies heading for a more targeted medicine, through the identification of genetic mechanisms of disease and therapeutic responses. Session I, chaired by Richard James (Geneva) and Guido Franceschini (Milano), on 'Basic mechanisms of action of drugs' highlighted molecular and cellular actions by which present (fibrates, statins) or future (ACAT or MTP inhibitors) drugs or hormones may modulate lipoprotein metabolism. Marten Hofker (Leiden) and Philippa Talmud (London) chaired Session II on 'Regulation of gene expression', which reported cellular regulations by nuclear receptors (PPARs), or the regulation of lipid trafficking by membrane receptors (SR-BI, Megalin, Apo-E receptor, scavenger receptors) or by intracellular (IFN gamma signalling pathways) or extracellular proteins (lipases). Beyond gene expression, Session III, 1st part, entitled 'Lipoprotein modifying enzymes' was chaired by Katriina Aalto-Setälä (Tampere). Roles of lipases (HL, LPL) and transfer proteins (CETP, PLTP), as well as structures of lipid binding molecules (LCAT, apolipoproteins), were further explored. The 'Gene interactions' session chaired by Rudolph Poledne (Prague), and 'Novelties' chaired by Hans Dieplinger (Innsbruck), reported elegant models of cross-bred, tissue specific knock-out or YAC-transgenic mice for lipoprotein metabolism, and descriptions of gene interactions in polygenic disorders or new loci for familial lipid disorders (familial combined hyperlipidemia, metabolic syndrome and Tangier disease) in humans.

Animals↗
PubMed1998

European Lipoprotein Club: report of the 20th annual conference, Tutzing, 8-11 September 1997.

The year 1997 celebrated the 20th anniversary of the European Lipoprotein Club. Sessions explored topics in the line of classical concepts and forthcoming advances in the field of basic and clinical research on lipoproteins. Participants from 18 European countries attended the conference. Recent Developments in Lipoprotein Research, were reviewed by Thomas Olivecrona (Umea, Sweden), who gave a perspective on lipolysis; and Gerd Assmann (Münster, Germany), who overviewed epidemiological data of the PROCAM study and focused on the biochemical and genetic components of reverse cholesterol transport. Session I, chaired by Katriina Aalto Setälä (Tampere, Finland) and Marten Hofker (Leiden, Netherlands) was dedicated to 'Lipoprotein receptors (old and new)'. Various structural and functional aspects were reported for the newcomers in the ever enriching LDL receptor gene family (VLDLR, LR7/8B, LR11, Megalin, RAP-related proteins). However, a decade of identification of LDL receptors gene defects reveals now that phenocopies of familial hypercholesterolemia may be linked to a third, yet unknown locus. Identification of pathways which clear HDL is underway. Session II, chaired by David Bowyer (Cambridge, United Kingdom) and Richard W James (Geneva, Switzerland), was entitled 'Significance of lipoprotein heterogeneity (metabolic and pathological aspects)'. Factors involved in lipoprotein modification (dense LDL, oxidation), transient production (post prandial, VLDL synthesis) or degradation (complement activation) and controversial hypotheses on their links with atherosclerosis were discussed. Session III on 'Novel methodologies for lipoprotein research' was chaired by Rudolph Poledne (Prague, Czech Republic) and Armin Steinmetz (Marburg, Germany). Simple technologies for routine assessment of lipoprotein metabolism, as well as the most sophisticated ones, to study lipid and free radical exchanges between particles, were presented.

Electrophoresis, Capillary↗
PubMed1998

Genetic risk factors and ischaemic cerebrovascular disease: role of common variation of the genes encoding apolipoproteins and angiotensin-converting enzyme.

DNA polymorphisms in genes encoding apolipoproteins (apo) A-I, C-III, B and E and angiotensin-converting enzyme (ACE) have been proposed to be associated with the risk of coronary artery disease (CAD). We studied whether the same genetic markers would also be associated with the occurrence and extent of atherosclerosis in cervical arteries. DNA samples from 234 survivors of stroke or a transient ischaemic attack aged 60 years or less were examined. The presence of atherosclerosis was assessed using aortic arch angiograms. The SstI polymorphism of apoA-I/C-III gene locus, the XbaI polymorphism of apoB gene, common apoE phenotypes and the insertion/deletion polymorphism of the ACE gene were analysed. The allele frequencies of the apoA-I/C-III, apoB, apoE or ACE gene did not differ between the groups with (n = 148) or without (n = 85) cervical atherosclerosis. However, when patients with at least one apoE4 allele and one X2 allele of apoB were combined and compared with those without either of them (E2E3 or E3E3 and X1X1), a significant association with the presence of cervical atherosclerosis was found (P = 0.03). The patients having the E2E3 phenotype had a significantly elevated serum triglyceride level compared with those with the E3E3 phenotype (P = 0.03). Serum high-density lipoprotein (HDL) cholesterol was lower in the patients with the E2E3 phenotype than in those with the E3E3 and E3E4 (P = 0.01 and P = 0.06, respectively). The apoB or ACE genotypes were not significantly associated with serum lipid or lipoprotein levels. There was no association between the ACE gene polymorphism and the occurrence of hypertension. In conclusion, the interaction of common apoB and apoE alleles may increase the risk of atherosclerosis in cervical arteries.

Alleles↗
PubMed1997

Gene therapy of single-gene disorders: preface to the special section.

Gene therapy was introduced into clinical practice with great excitement, much publicity and considerable optimism in the early 1990s. Scientific evaluation of the early clinical trials has, however, greatly reduced the initial optimism. Follow-up studies have revealed that many early gene therapy trials mainly represented gene transfer into patients, possibly with short-term effects, but not true gene therapy where the course of the disease is permanently affected. This has lead to critical re-evaluation of the approaches taken. Clearly, more basic understanding is needed of the molecular mechanisms of the diseases treated. For this purpose, better animal models for human diseases are necessary. One of the biggest obstacles for gene therapy has been the lack of adequate vector systems. Development of new vectors for efficient and targeted delivery and uptake of therapeutic genes is a crucial area where progress needs to be made. The rationale for gene therapy depends largely on the type of disease to be treated. Recessively inherited single-gene disorders represent diseases where the concept of gene therapy--addition of a therapeutic gene to restore the lost function of two mutant alleles--is easily understood and rarely questioned. However, most gene therapy protocols are focused on multifactorial diseases such as malignancies where the therapeutic approach is quite different. While gene transfer technologies are being developed into truly effective gene therapy, the fight against inherited single-gene disorders also continues at population level by carrier screening and prenatal diagnostics where rapid methodological developments are taking place.

Alleles↗
PubMed1996

Further characterization of the metabolic properties of triglyceride-rich lipoproteins from human and mouse apoC-III transgenic mice.

We previously showed that human apoC-III expression in transgenic mice causes hypertriglyceridemia due to the accumulation of enlarged very low density lipoprotein (VLDL)-like particles, with increased triglycerides and apoC-III and decreased apoE. In vivo turnover studies indicated the metabolic basis was decreased particle fractional catabolic rate. The presence of enlarged triglyceride-rich particles with prolonged residence time in plasma implied defective lipolysis, but in vitro these particles were good substrates for purified lipoprotein lipase (LPL). In the current study we further characterize the metabolic properties of these particles. We show that expression of a mouse apoC-III transgene can also cause hypertriglyceridemia with a similar accumulation of a VLDL-like particle with increased apoC-III and decreased apoE. A vitamin A fat tolerance test was used to show that MoCIIITg and HuCIIITg mice had similarly delayed clearance of triglyceride-rich postprandial particles. Thus, the previously observed hypertriglyceridemia caused by human apoC-III transgene expression was not due interspecies incompatibility but a property of apoC-III. In further experiments we showed VLDL from apoC-III transgenic mice interacted poorly with fibroblast lipoprotein receptors and this could be corrected by adding exogenous apoE. In addition, control VLDL interaction could be decreased by exogenous apoC-III. Moreover, the hypertriglyceridemia of HuCIIITg mice could be normalized by crossbreeding with HuETg mice. Thus, a functionally significant reciprocal relationship of apoC-III and apoE exists, presumably due to competition for space on the surface of triglyceride-rich lipoproteins. Finally, VLDL from HuCIITg and MoCIIITg mice showed decreased binding to heparin-Sepharose. This suggests and additional locus of the defect in these mice could potentially be in the binding of triglyceride-rich lipoproteins to heparan sulfate proteoglycan matrix on the surface of endothelial cells in which LPL is embedded. This could explain the predicted functional lipase deficiency in apoC-III transgenic mice based on the observation of a prolonged residence time of enlarged triglyceride-rich lipoproteins.

Animals↗
PubMed1995

Severe hypertriglyceridemia, reduced high density lipoprotein, and neonatal death in lipoprotein lipase knockout mice. Mild hypertriglyceridemia with impaired very low density lipoprotein clearance in heterozygotes.

Lipoprotein lipase (LPL)-deficient mice have been created by gene targeting in embryonic stem cells. At birth, homozygous knockout pups have threefold higher triglycerides and sevenfold higher VLDL cholesterol levels than controls. When permitted to suckle, LPL-deficient mice become pale, then cyanotic, and finally die at approximately 18 h of age. Before death, triglyceride levels are severely elevated (15,087 +/- 3,805 vs 188 +/- 71 mg/dl in controls). Capillaries in tissues of homozygous knockout mice are engorged with chylomicrons. This is especially significant in the lung where marginated chylomicrons prevent red cell contact with the endothelium, a phenomenon which is presumably the cause of cyanosis and death in these mice. Homozygous knockout mice also have diminished adipose tissue stores as well as decreased intracellular fat droplets. By crossbreeding with transgenic mice expressing human LPL driven by a muscle-specific promoter, mouse lines were generated that express LPL exclusively in muscle but not in any other tissue. This tissue-specific LPL expression rescued the LPL knockout mice and normalized their lipoprotein pattern. This supports the contention that hypertriglyceridemia caused the death of these mice and that LPL expression in a single tissue was sufficient for rescue. Heterozygous LPL knockout mice survive to adulthood and have mild hypertriglyceridemia, with 1.5-2-fold elevated triglyceride levels compared with controls in both the fed and fasted states on chow, Western-type, or 10% sucrose diets. In vivo turnover studies revealed that heterozygous knockout mice had impaired VLDL clearance (fractional catabolic rate) but no increase in transport rate. In summary, total LPL deficiency in the mouse prevents triglyceride removal from plasma, causing death in the neonatal period, and expression of LPL in a single tissue alleviates this problem. Furthermore, half-normal levels of LPL cause a decrease in VLDL fractional catabolic rate and mild hypertriglyceridemia, implying that partial LPL deficiency has physiological consequences.

Adipose Tissue↗
PubMed1994

Variability gene effects of DNA polymorphisms at the apo B, apo A I/C III and apo E loci on serum lipids: the Cardiovascular Risk in Young Finns Study.

We studied the influence of selected genetic markers on the intra-individual long-term variability in serum lipid levels. The study cohort consisted of a sub-sample from a large follow-up study of atherosclerosis precursors in children and young adults. A total of 320 subjects had determinations of apo B XbaI RFLP genotypes, 305 subjects had apo AI/CIII SstI RFLP genotype determinations and 1581 subjects had their apo E phenotypes determined. Complete data on serum lipids were available at 3-year intervals over a 6-year follow-up period. The subjects were healthy and aged 3-18 years at baseline. Intra-individual variability was assessed with a nested analysis of variance procedure. Each of the genetic markers studied here significantly affected intra-individual variability of serum lipid levels. No clear sex influence was observed, although the differences in variability tended to be more significant in males. Apo B XbaI genotypes significantly influenced intra-individual variability of total and LDL-cholesterol levels in both sexes. A marked effect of the XbaI genotype was also found on triglyceride variability. In males the standardized intra-individual triglyceride variances were 0.71 and 0.34 in genotypes X1X1 and X2X2, respectively (p < 0.001), with a clear gene dosage effect. The apo AI/CIII genotype had an influence only on the variability of total cholesterol and LDL-cholesterol levels and only in males. The apo E phenotypes were associated with intra-individual variability in total and LDL-cholesterol levels but again, only in males.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Intestinal expression of human apolipoprotein A-IV in transgenic mice fails to influence dietary lipid absorption or feeding behavior.

Two transgenic mouse lines, expressing low or high amounts of human apo A-IV were created. In low and high expressor HuAIVTg mice on a chow diet, serum human apo A-IV levels were 6 and 25 times the normal human level and on a high fat diet, they were 12 and 77 times higher. Human apo A-IV was equally distributed between lipoprotein (mainly HDL) and lipid-free fractions. Intestinal absorption of radiolabeled cholesterol and triglycerides was unaffected in HuAIVTg mice. Vitamin A, carried exclusively in chylomicrons and their remnants, was catabolized normally. When an intragastric vitamin E bolus is given to the HuAIVTg mice, the initial absorption and appearance in triglyceride-rich lipoproteins was similar to that observed in normal mice. However, elevated amounts of vitamin E were subsequently observed in the VLDL of the HuAIVTg mice. Furthermore, in the fed state, serum VLDL triglycerides were markedly elevated in HuAIVTg mice. This effect was greater in high expressor mice. Serum total cholesterol was not elevated, but the distribution was altered in the HuAIVTg mice; VLDL-C was increased at the expense of VLDL-C. Kinetic studies suggested a delayed clearance of VLDL in HuAIVTg mice. Apo A-IV has been suggested to be a satiety factor, but no effect on feeding behavior or weight gain was observed in these HuAIVTg mice. In summary, our studies with HuAIVTg mice show that additional apo A-IV does not effect intestinal absorption of fat and fat-soluble vitamins, and at least chronic elevation of plasma apo A-IV does not effect feeding behavior in this model system.

Animals↗
PubMed1993

Dietary fat increases high density lipoprotein (HDL) levels both by increasing the transport rates and decreasing the fractional catabolic rates of HDL cholesterol ester and apolipoprotein (Apo) A-I. Presentation of a new animal model and mechanistic studies in human Apo A-I transgenic and control mice.

In humans, diets high in saturated fat and cholesterol raise HDL-cholesterol (HDL-C) levels. To explore the mechanism, we have devised a mouse model that mimics the human situation. In this model, HuAITg and control mice were studied on low fat (9% cal)-low cholesterol (57 mg/1,000 kcal) (chow) and high fat (41% cal)-high cholesterol (437 mg/1,000 kcal) (milk-fat based) diets. The mice responded to increased dietary fat by increasing both HDL-C and apo A-I levels, with a greater increase in HDL-C levels. This was compatible with an increase in HDL size observed by nondenaturing gradient gel electrophoresis. Turnover studies with doubly labeled HDL showed that dietary fat both increase the transport rate (TR) and decreased the fractional catabolic rate of HDL cholesterol ester (CE) and apo A-I, with the largest effect on HDL CE TR. The latter suggested that dietary fat increases reverse cholesterol transport through the HDL pathway, perhaps as an adaptation to the metabolic load of a high fat diet. The increase in apo A-I TR by dietary fat was confirmed by experiments showing increased apo A-I secretion from primary hepatocytes isolated from animals on the high fat diet. The increased apo A-I production was not associated with any increase in hepatic or intestinal apo A-I mRNA, suggesting that the mechanism of the dietary fat effect was posttranscriptional, involving either increased translatability of the apo A-I mRNA or less intracellular apo A-I degradation. The dietary fat-induced decrease in HDL CE and apo A-I fractional catabolic rate may have been caused by the increase in HDL particle size, as was suggested by our previous studies in humans. In summary, a mouse model has been developed and experiments performed to better understand the paradoxical HDL-raising effect of a high fat diet.

Animals↗
PubMed1992

Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells.

apoE-deficient mice have been created by homologous recombination in ES cells. On a low fat, low cholesterol chow diet these animals have plasma cholesterol levels of 494 mg/dl compared with 60 mg/dl in control animals, and when challenged with a high fat Western-type diet, these animals have plasma cholesterol levels of 1821 mg/dl compared with 132 mg/dl in controls. This marked hypercholesterolemia is primarily due to elevated levels of very low and intermediate density lipoproteins. At 10 weeks of age, apoE-deficient mice have already developed atherosclerotic lesions in the aorta and coronary and pulmonary arteries. apoE-deficient mice are a promising small animal model to help understand the role of apoE in vivo and the genetic and environmental determinants of atherosclerosis.

Animals↗
PubMed1992

Characterization of the mouse apolipoprotein Apoa-1/Apoc-3 gene locus: genomic, mRNA, and protein sequences with comparisons to other species.

In this report we present the genomic, cDNA, and predicted protein sequences for mouse apolipoproteins A-I and CIII, as well as sequence comparisons with other species. The genes for these apolipoproteins are within 2.5 kb of each other and convergently transcribed. The almost 9 kb of genomic sequence presented extends from 1298 bp 5' to the apolipoprotein A-I (Apoa-1) gene to 1249 bp 5' to the apolipoprotein CIII (Apoc-3) gene. The mouse Apoa-1 gene is 1.76 kb in length with four exons and three introns. The 5' flanking region contains TATA and CCAAT box sequences, an interferon responsive element homology, and potential binding sites for transcription factors CTF/NF1 and HNF4. Translation of the cDNA predicts that the mouse Apoa-1 primary transcript is 264 amino acids. The mouse Apoc-3 gene is 2.2 kb in length and also consists of four exons and three introns. The 5' flanking region contains TATA and CCAAT box sequences, RXR-1 and ARP-1 binding sites, and potential binding sites for transcription factors HNF4, NFkB, AP-1, and CTF/NF1. Translation of the cDNA predicts that the mouse Apoc-3 primary transcript is 99 amino acids. The clustering and genomic organization of the mouse Apoa-1 and Apoc-3 genes are similar to those of the rat and human genes. Significant sequence homologies between species exist for the proximal promoter and exonic regions of each gene, but not for the intronic or intergenic regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Prevalence and geographical distribution of major LDL receptor gene rearrangements in Finland.

In order to determine the prevalence of major rearrangements of the low density lipoprotein (LDL) receptor gene in Finland, DNA samples of 199 unrelated Finnish patients with the heterozygous form of familial hypercholesterolaemia (FH) were examined by Southern blot analysis. The FH-Helsinki mutation, characterized by a 9.5-kb deletion in the 3'-end of the LDL receptor gene, was found in 75 (38%) of the patients. The prevalence of this mutation ranged from 26-58% in different areas of Finland. A striking exception was the North Karelia region, where only one out of 26 (4%) FH patients was found to carry the FH-Helsinki allele. Two patients were found to carry other types of large nucleotide rearrangements of the LDL receptor gene. One mutation was a 7.5-kb deletion eliminating exons 7 to 10, and the other was a 13-kb deletion covering exons 11 to 16 of the LDL receptor gene. Serum lipoprotein levels were very similar in each category of mutation, i.e. in patients with the FH-Helsinki gene, those with the two other types of deletion, and the remaining patients with as yet unknown types of LDL receptor gene defects. These results show that, even in genetically uniform populations, FH may be heterogeneous at the DNA level. DNA techniques enable an unequivocal diagnosis for almost 40% of the Finnish patients with the heterozygous form of FH.

Blotting, Southern↗