[Epidemiology of age related macular degeneration]. / Epidémiologie de la dégénérescence maculaire liée à l'âge.

Age-related macular degeneration (ARMD) is a multifactorial and polygenic disease and is the main cause of vision loss in developed countries. The environmental factors of ARMD can modify prevalence and incidence of this disease. This article is a review of the main environmental factors currently recognized as at risk or protective factor for ARMD. Modification of these factors is of crucial importance because it could delay the onset of exudative or atrophic forms of the disease.

Nutritional AMD treatment phase I (NAT-1): feasibility of oral DHA supplementation in age-related macular degeneration.

PURPOSE: To create a pilot study in order to evaluate the feasibility of a prospective case-control study of oral supplementation with fish oil (docosahexaenoic acid [DHA]; eicosapentaenoic acid [EPA]) in a population with age-related macular degeneration (AMD). METHODS: A homogeneous group of 38 patients with drusenoid pigment epithelial detachment in one eye (PED) without choroidal new vessels (CNV) was selected. A complete ophthalmologic examination, and a complete profile of fatty acids in serum (S) and in red blood cell membranes (RBCM), were recorded at day 0 and month 6. In group 1, 22 patients were orally supplemented with EPA (720 mg/day) and DHA (480 mg/day) during 6 months. In group 2, 16 patients were followed as controls. Nutritional recommendations on fish consumption were given to both groups. RESULTS: In group 1, after 6 months supplementation we observed a significant blood enrichment in EPA (EPA-S: 2.20 vs 0.79, p<0.0001 and EPA-RBCM: 2.24 vs 0.85, p<0.0001) and in DHA (DHA-S: 2.47 vs 1.56, p<0.0001 and DHA-RBCM: 6.47 vs 4.67, p<0.0001). No change was observed in group 2 despite nutritional recommendations. In this short followup, no evolution to CNV was noted in either of the two groups. Neither side effects nor dropouts were observed in either of the groups. DISCUSSION: This study supports the feasibility of a long-term double-masked prospective case-control study in an AMD population in order to evaluate a potential benefit from oral supplementation with DHA.

Age and origin of major Smith-Lemli-Opitz syndrome (SLOS) mutations in European populations.

BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) (MIM 270 400) is an autosomal recessive multiple congenital anomalies/mental retardation syndrome caused by mutations in the Delta7-sterol reductase (DHCR7, E.C.1.3.1.21) gene. The prevalence of SLOS has been estimated to range between 1:15000 and 1:60000 in populations of European origin. METHODS AND RESULTS: We have analysed the frequency, origin, and age of DHCR7 mutations in European populations. In 263 SLOS patients 10 common alleles (c.964-1G>C, p.Trp151X, p.Thr93Met, p.Val326Leu, p.Arg352Trp, p.Arg404Cys, p.Phe302Leu, p.Leu157Pro, p.Gly410Ser, p.Arg445Gln) were found to constitute approximately 80% of disease-causing mutations. As reported before, the mutational spectra differed significantly between populations, and frequency peaks of common mutations were observed in North-West (c.964-1G>C), North-East (p.Trp151X, p.Val326Leu) and Southern Europe (p.Thr93Met). SLOS was virtually absent from Finland. The analysis of nearly 8000 alleles from 10 different European populations confirmed a geographical distribution of DHCR7 mutations as reported in previous studies. The common Null mutations in Northern Europe (combined ca. 1:70) occurred at a much higher frequency than expected from the reported prevalence of SLOS. In contrast the most common mutation in Mediterranean SLOS patients (p.Thr93Met) had a low population frequency. Haplotypes were constructed for SLOS chromosomes, and for wild-type chromosomes of African and European origins using eight cSNPs in the DHCR7 gene. The DHCR7 orthologue was sequenced in eight chimpanzees (Pan troglodytes) and three microsatellites were analysed in 50 of the SLOS families in order to estimate the age of the three major SLOS-causing mutations. CONCLUSIONS: The results indicate a time of first appearance of c.964-1G>C and p.Trp151X some 3000 years ago in North-West and North-East Europe, respectively. The p.Thr93Met mutations on the J haplotype has probably first arisen approximately 6000 years ago in the Eastern Mediterranean. Together, it appears that a combination of founder effects, recurrent mutations, and drift have shaped the present frequency distribution of DHCR7 mutations in Europe.

[Blood screening of glucose and lipid disorders as coronary atherosclerosis risks factors in French adolescents 16 to 19-20 years old]. / Dépistage des anomalies sanguines glucidolipidiques à risque coronarien, de 16 à 19-20 ans. A propos d'une enquête menée chez 599 jeunes volontaires.

A screening of fasting blood glucose and lipids disorders, presumely linked to premature atherosclerosis namely affecting Coronary arteries, has been performed among 599 adolescents of both sexes with the goal of establishing the actual prevalence of these disorders in French population recruited through different areas of the country. All of them were between ages of 16 and 19-20 years old, and invited to give, in total gratuity, their blood samples to private and accreditable laboratories close to their living habitation. After 262 exclusions due to either previous screening not signaled before or present use of contraceptive pill in girls, only 202 boys and 135 girls remained eligible for such a prevalence study. Using plasma enzymatic dosages of CT, HDL C, (calculated) LDLC, TG, and blood glucose, cut off points for each of these parameters, were analysed as well as calculated international index of CT/HDLC and CT minus HDLC. But the first one index was shown the best tool for the final estimation of the frequency of lipid disorders, which requires primary prevention. Indeed, despite of a rather high frequency of overlaps of CT and LDLC respectively found at 16.3 and 22.5% for boys, and 27.3 and 27.5% for girls, the still higher increase of frequency of HDL C at 31% for boys and 28.1% for girls has shown a very significant compensation of these previous increases. In such a way as the authentic prevalence of atherogenic lipid disorders is found reduced in boys to 8.4% and in girls to 7.4% for CT/HDLC>/=4.5 ratio, and to 5.4% in boys and 5.2% in girls for CT less HDLC. A Familial Dominant Hypercholesterolemia was discovered only two times in two girls 16 years old. Other abnormal lipid profiles were rather those of Mixed H., type IV, chiefly mild Hypercholesterolemia, and some rare cases of HypoHDLemia. The only greater linked cardiovascular risk factor was direct parental C.V. heredity, round 30% among lipid disorders. Obesity remained rare, as well as Metabolic Syndrome in the present recruitment. Contraceptive pill increases significantly all lipid parameters and atherogenic index: chiefly CT minus HDLC which reaches almost the double of frequency (15%) versus that of girls without pill. But 53% of boys with proatherogenic lipid disorders are smokers, while only 10% of these dyslipidemic girls smoke.

Combined hyperlipidemia/hyperalphalipoproteinemia associated with premature spontaneous atherosclerosis in mice lacking hepatic lipase and low density lipoprotein receptor.

BACKGROUND AND METHODS: Hepatic lipase (HL) is an enzyme which hydrolyzes triglycerides from plasma lipoproteins and thus takes part in the metabolism of triglyceride-rich lipoprotein remnants and high density lipoproteins. The search described here concentrated on the description of the double invalidation of the HL and LDL receptor genes in mice in order to better understand the possible role of HL in combined hyperlipidemia/hyperalphalipoproteinemia and development of atherosclerosis. RESULTS: We show here that mice lacking both endogenous HL and LDL receptor (HL-/-:LDLR-/-) dramatically increased their plasma triglyceride-rich lipoproteins and their remnants as a consequence of reduced liver uptake. This result is strenghthened by the fact that HL-/-:LDLR-/- were found to overexpress LRP, LSR, and apoE genes. Interestingly, HL-/-:LDLR-/- mice showed premature spontaneous atherosclerosis and aortic lesions from 1-year-old animals were two-fold larger than those of LDLR-/- single mutants. We confirmed that HL-/- and wild-type mice did not develop atherosclerosis lesion even 1 year after birth. CONCLUSIONS: Analysis of this double HL-LDLR knockout mouse model provides in vivo evidence that HL has a major role in the clearance of TRL remnants when LDLR is deficient and in the reduction of the development of atherosclerosis.

Combination of apolipoprotein E2 and lipoprotein lipase heterozygosity causes severe hypertriglyceridemia during pregnancy.

Pregnancy is a physiological condition where plasma triglyceride levels are moderately increased. This results from raised synthesis of very-low-density lipoproteins (VLDL) in response to elevated estrogen levels. The occurrence of marked hypertriglyceridemia (HTG) is rare and may result from combination of heterozygote mutation in the lipoprotein lipase (LPL) gene and apolipoprotein E2 isoform, as reported in this case. This observation illustrates the interaction between genetic and environmental factors, since pregnancy may disclose a silent LPL deficiency. The risk of acute pancreatitis threatens both the mother and fetus lives. Early recognition of severe HTG and appropriate management are essential for a successful pregnancy outcome.

Major hypertriglyceridemia in HIV-infected patients on antiretroviral therapy: a role of the personal and family history.

BACKGROUND: Our aim was to identify factors predisposing HIV-infected patients on long-term antiretroviral therapy (ART) to major hypertriglyceridemia (HTG). PATIENTS AND METHODS: We conducted a retrospective, case-control study involving 76 HIV-infected patients with HTG, defined by 12-hour fasting plasma triglyceride (TG) > 4.5 mmol/l on at least one occasion, and 150 HIV-infected matched control patients with TG consistently below 1.8 mmol/l. RESULTS: Patients coinfected by the hepatitis C virus appeared to be protected from HTG. In addition to known predisposing factors for HTG in HIV-infected patients (ART and immune/viral status), patients with a history of excess body weight were twice as likely to have HTG (odds ratio [OR] 2.8, 95% confidence interval [CI]: 1.1-6.9); HTG was also more frequent in patients who had a first-degree relative with cardiovascular disease (CVD) or a major risk factor for CVD (OR = 3.6, CI: 1.3-9.9). CONCLUSION: By identifying subgroups of highly predisposed patients, appropriate lifestyle and dietary measures could be recommended on ART initiation.

Apolipoprotein E polymorphism, a marker of disease severity in primary biliary cirrhosis?

BACKGROUND/AIMS: To determine whether the apolipoprotein E (apo-E) polymorphism is associated with the risk of primary biliary cirrhosis (PBC), the severity of the disease and its response to ursodeoxycholic acid (UDCA) therapy. METHODS: The apo-E genotype was determined in 72 PBC patients. Genotype and allele distributions were compared with those found in the French general population. Laboratory parameters obtained before and after 1- and 4-year UDCA treatment were compared according to the apo-E allele carrier status. RESULTS: Apo-E allele and genotype distributions were similar between PBC patients and the general population. At the time of diagnosis, the epsilon4 allele carriers were younger (P < 0.05), had higher bilirubin (P < 0.05) and IgG (P < 0.001) levels and a lower prothrombin index (P < 0.01) than epsilon2 (homozygous + heterozygous) or epsilon3 homozygous allele carriers. After 4-year UDCA therapy, the decrease in serum alkaline phosphatase and in alanine and aspartate aminotransferase activities was lower in percentage in the epsilon4 than in other epsilon allele carriers (P < 0.01). CONCLUSIONS: Although apo-E polymorphism does not appear to confer susceptibility to PBC, it probably influences PBC progression and response to UDCA. The epsilon4 allele may identify patients with high risk of severe disease and poor response to treatment.

Apolipoprotein B Arg3500Gln mutation prevalence in children with hypercholesterolemia: a French multicenter study.

BACKGROUND: Familial defective apolipoprotein B-100, a dominantly inherited form of hypercholesterolemia caused by a single Arg3500Gln mutation, is silent in childhood but may confer a high risk of cardiovascular disease in adulthood. The objective was to determine the prevalence of familial defective apolipoprotein B-100 in hypercholesterolemic French children and to provide a basis for targeting screening efforts in this population. METHODS: One hundred ninety children attending 13 pediatric clinics distributed throughout France were included based on the presence of type IIa hypercholesterolemia with a plasma low-density lipoprotein-cholesterol level of more than 130 mg/dL. The Arg3500Gln mutation was detected in dried blood spots using a polymerase chain reaction assay combined with enzymatic restriction. RESULTS: Three hyperlipidemia phenotypes were found: monogenic dominant pure hypercholesterolemia (n = 117), polygenic hypercholesterolemia (n = 43), and combined hyperlipidemia (n = 11). Three unrelated children were heterozygous for the Arg3500Gln mutation; all three had monogenic dominant pure hypercholesterolemia (3/94 families; 3.2%), yielding a prevalence of 1.83% (3/164) in hypercholesterolemic children, which is similar to prevalences reported in European adults. CONCLUSIONS: The familial defective apolipoprotein B-100 mutation was common (1/31) in children with a phenotype of familial hypercholesterolemia, supporting screening in this population with the goal of preventing premature cardiovascular events.

[New progress and new tools for the study of molecular genetics in dyslipoproteinemia]. / Nouveaux progrès et nouveaux outils d'étude de la génétique moléculaire des dyslipoprotéinémies.

More than three centuries after Mendel, at the era of electronic and computed information taking over the principle of information transmitted in discrete "packets" on the "internet", the sequence of the human genome is about to be completely released on public databases accessible on that very same internet. The gene, classically a virtual object, has become after several decades of intensive progress in cellular and molecular biology, a real object commonly manipulated and analyzed. More than fifty genes have been identified in the regulation of lipoprotein metabolism, giving rise to novel molecular pathophysiological bases for dyslipoproteinemia and beyond to other disorders related with lipid homeostasis. Dyslipoproteinemia, or disorders of lipoprotein metabolism commonly considered as lifestyle and age-related diseases, have now a molecular basis. Novel clinical entities no longer defined as "essential", but as molecular-based are progressively individualized. Novel tools for the diagnosis, prognosis or treatment have already modified the way these silent and frequent diseases are managed in clinical practice. In that respect, dyslipoproteinemia are among pioneer diseases in the medicine of the new millennium, which progressively evolves from a fact-based medicine to the individualized prevention of morbid events.

Fh-Souassi: a founder frameshift mutation in exon 10 of the LDL-receptor gene, associated with a mild phenotype in Tunisian families.

Familial hypercholesterolemia (FH) has a higher prevalence in central Tunisia together with a milder clinical expression than in western countries. The molecular basis of FH in Tunisia remains unknown. Our aim was to identify FH-causing mutations in three unrelated families (21 subjects) from the area of Souassi (central Tunisia). In probands with a presentation of homozygous FH, the promoter and 18 exons of the low density lipoprotein (LDL)-receptor gene were sequenced in both orientations. A novel complex frameshift mutation was identified in exon 10, nucleotides 1477-1479 (TCT) at Serine 472 were replaced by an insertion of seven nucleotides (AGAGACA), producing a premature termination codon 43 amino acids downstream. Binding of 125I-labelled LDL at 4 degrees C to cultured fibroblasts from two probands showed <2% normal LDL-receptor activity. AvaII digestion of PCR amplified genomic DNA identified this unique mutation in all families; homozygotes n=11, heterozygotes n=10. All mutation carriers shared the same haplotype (7 RFLPs), suggesting that they had a common ancestor. Despite high plasma LDL levels (m=16.0+/-3.0 mmol/l) and extravascular cholesterol deposits, most homozygotes were diagnosed after puberty and had a delayed onset of cardiovascular complications. Moreover, most heterozygotes were free of clinical signs and had plasma LDL cholesterol in the normal range (4.7+/-1.3 mmol/l) without taking any lipid-lowering medication. This mild clinical phenotype which contrasted with the severity of the mutation, could not be explained by specific apolipoprotein E or lipoprotein lipase alleles.

Comparison of a new method for the direct and simultaneous assessment of LDL- and HDL-cholesterol with ultracentrifugation and established methods.

BACKGROUND: Automated electrophoresis combined with enzymatic cholesterol staining might improve routine assessment of LDL- and HDL-cholesterol (LDLC and HDLC), as an alternative to the Friedewald equation and precipitation. A new method (Hydrasys; SEBIA) that adapts the cholesterol esterase/cholesterol oxidase reaction within urea-free gels was evaluated. METHODS: Fresh sera from 725 subjects (512 dyslipidemics) were analyzed by electrophoresis, in parallel with sequential ultracentrifugation, beta-quantification, calculation, and precipitation. RESULTS: Electrophoresis was linear up to 4 g/L cholesterol, with a detection limit of 0.042 g/L cholesterol/band. Within-run, between-run, between-batch, and between-operator imprecision (CVs) were 1.6%, 2.0%, 1.5%, and 2.7% for LDLC, and 3.9%, 4.3%, 5.5%, and 4.9% for HDLC, and remained unchanged up to 6.3 g/L plasma triglycerides (TGs). Precision decreased with very low HDLC (<0.25 g/L). Serum storage for 3-7 days at +4 or -80 degrees C did not interfere significantly with the assay. Agreement with beta-quantification was stable for LDLC up to 5.07 g/L (r = 0.94), even at TG concentrations >4 g/L (r = 0.91). Bias (2.88% +/- 12%) and total error (7.84%) were unchanged at TG concentrations up to 18.5 g/L. Electrophoresis predicted National Cholesterol Education Program cut-points with <0.04 g/L error, exactly and appropriately classified 79% and 96% of the subjects, and divided by 2.4 (all subjects) and 5.8 (TGs >1.5 g/L) the percentage of subjects underestimated by calculation. One-half of the patients with TGs >4 g/L had LDLC >1.30 g/L. For HDLC, correlation was better with precipitation (r = 0.87) than ultracentrifugation (r = 0.76). Error (-0.10% +/- 26%) increased when HDLC decreased (<0.35 g/L). Direct assessment of the LDLC/HDLC ratio detected 45% more high-risk subjects than the calculation/precipitation combination. CONCLUSIONS: Electrophoresis provides reliable quantification of LDLC, improving precision, accuracy, and concordance over calculation, particularly with increasing plasma TGs. Implementation of methods to detect low cholesterol concentrations could extend the applications for HDLC assessment.

Classical LCAT deficiency resulting from a novel homozygous dinucleotide deletion in exon 4 of the human lecithin: cholesterol acyltransferase gene causing a frameshift and stop codon at residue 144.

Lecithin: cholesterolacyltransferase (LCAT) transacylates the fatty acid at the sn-2 position of lecithin to the 3beta-OH group of cholesterol forming lysolecithin and the majority of cholesteryl ester found in plasma. LCAT participates in the reverse cholesterol transport pathway in man where it esterifies tissue-derived cholesterol following efflux from peripheral cells into HDL. Only 38 unique mutations in the human LCAT gene have been reported worldwide. Our French female proband presented with corneal opacity and no detectable plasma LCAT activity using either endogenous or exogenous assays. Her total plasma cholesterol and HDL cholesterol were low (2.34 mmol/l and 0.184 mmol/l, respectively) with a very high cholesterol/cholesteryl ester molar ratio (10.9:1). Plasma triglycerides were 0.470 mmol/l with low apo B (40.5 mg/dl), apo A-I (14.7 mg/dl), apo A-II (6.8 mg/dl) and apo E (2.1 mg/dl) levels. Plasma lipoprotein analysis by ultracentrifugation showed very low HDL concentrations and a characteristic shift of the lipoprotein profile towards larger, less dense particles. No proteinuria, renal dysfunction or signs of atherosclerosis were noted at age 45. Sequence analysis of her LCAT gene showed a novel homozygous TG-deletion at residues 138-139 that resulted in a frameshift causing the generation of a stop codon and premature termination of the LCAT protein at amino acid residue 144. Western blotting of the patient's plasma using a polyclonal IgY primary antibody against human LCAT failed to demonstrate the presence of a truncated LCAT protein. A 53 bp mismatched PCR primer was designed to generate an Fsp 1 restriction site in the wild type sequence of exon 4 where the mutation occurred. The 155 bp PCR product from the wild type allele produced a 103 bp and 52 bp fragment with Fsp 1 and no cleavage products with the mutant allele thus permitting rapid screening for this novel mutation.

Apolipoprotein A-I kinetics in heterozygous familial hypercholesterolemia: a stable isotope study.

Heterozygous familial hypercholesterolemia (FH) is associated with a moderate decrease of plasma apoA-I and HDL-cholesterol levels. The aim of the study was to test the hypothesis that these abnormalities were related to an increase of HDL-apoA-I fractional catabolic rate (FCR). We performed a 14-h infusion of [5,5,5-(2)H(3)]leucine in seven control subjects and seven heterozygous FH patients (plasma total cholesterol 422 +/- 27 vs. 186 +/- 42 mg/dL, P < 0.001, respectively). Plasma apoA-I concentration was not changed in FH compared to controls (respectively 115 +/- 18 vs. 122 +/- 15 mg/dL, NS), and HDL-cholesterol level was decreased (37 +/- 7 vs. 46 +/- 19 mg/dL, NS). Kinetics of HDL metabolism were modeled as a single compartment as no differences were observed between HDL(2) and HDL(3) subclasses. Both mean apoA-I FCR and absolute production rate (APR) were increased in FH (respectively, 0.36 +/- 0.14 vs. 0.22 +/- 0.05 pool/d, P < 0.05, and 18.0 +/- 7.7 and 11.2 +/- 2.3 mg/kg/d, P < 0.05). Higher HDL-triglyceride and HDL-apoE levels were observed in patients with heterozygous FH. (Respectively 19 +/- 8 vs. 8 +/- 3 mg/dL, P < 0.05, and 5.3 +/- 0.8 vs. 3.7 +/- 0.9 mg/dL, P < 0.05). We conclude that the catabolism of HDL-apoA-I is increased in heterozygous FH patients. However, plasma apoA-I concentration was maintained because of an increased HDL-apoA-I production rate.

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.

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.

The epsilon4 allele of the apolipoprotein E gene as a potential protective factor for exudative age-related macular degeneration.

PURPOSE: Apolipoprotein E (ApoE) is a polymorphic protein that plays a central part in plasma metabolism of lipids and in central nervous system lipid homeostasis. Our purpose was to evaluate the potential role of ApoE polymorphism in the occurrence of exudative age-related macular degeneration associated with drusen, which contain lipids. METHODS: We analyzed apolipoprotein E genotypes in 116 unrelated patients with exudative age-related macular degeneration in one eye and hard drusen (n = 39) or soft drusen (n = 77) in the other eye, and compared the results with those of age-matched and sex-matched control subjects (n = 168). Apolipoprotein E alleles were detected by a ploymerase chain reaction-based method. RESULTS: A lower frequency of the epsilon4 allele carriers was observed in the exudative age-related macular degeneration group compared with control subjects (12.1% vs 28.6%, respectively; P < .0009). The epsilon4 allele was less frequent in the age-related macular degeneration group compared with control subjects (0.073 vs 0.149, respectively; P < .006). This decreased frequency of the epsilon4 allele was mainly observed in the soft drusen subgroup compared with control subjects (0.045 vs 0.149, respectively; P < .0009). CONCLUSION: This lower relative frequency of the epsilon4 allele supports the hypothesis that the ApoE gene is a genetic protective factor identified in age-related macular degeneration.