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Biomedical subjects

M J Malloy

Publications and source records attributed to M J Malloy.

At least 19 recordsLinked to original sources
PubMed2000

Lack of association of lipoprotein(a) levels with coronary calcium deposits in asymptomatic postmenopausal women.

OBJECTIVES: This study sought to determine the relationship of lipoprotein(a) (Lp(a)) and other cardiac risk factors to coronary atherosclerosis as measured by calcification of coronary arteries in asymptomatic postmenopausal women. BACKGROUND: Lipoprotein(a) is considered a risk factor for coronary heart disease. Coronary calcium deposition is believed to be a useful noninvasive marker of coronary atherosclerosis in women. However, to our knowledge, there are no reports of the relationship of Lp(a) to coronary calcium in postmenopausal women. METHODS: In 178 asymptomatic postmenopausal women (64 +/- 8 years), we measured Lp(a) and other cardiac risk factors: age, hypertension, diabetes, low-density lipoprotein cholesterol, smoking status, body mass index, physical activity level and duration of hormone replacement therapy. Electron-beam computed tomography was done to measure coronary calcium (calcium score). We analyzed the relationship between calcium score and cardiac risk factors using multivariate analysis. RESULTS: Although calcium score correlated with traditional risk factors of age, diabetes, hypertension and smoking, it did not correlate with Lp(a) in the asymptomatic postmenopausal women. Similar multivariate analyses were done in the subjects age >60 years and in the subjects with significant coronary calcium deposit (calcium score > or =50). These analyses also have failed to show an association of levels of Lp(a) with coronary calcium deposits. CONCLUSIONS: We conclude that in asymptomatic postmenopausal women, Lp(a) levels do not correlate with coronary atherosclerosis as measured by coronary calcium deposits.

Adult↗
PubMed1999

Human renin gene BglI dimorphism associated with hypertension in two independent populations.

The renin (REN) gene is a good candidate that could underlie an individual's genetic susceptibility to human essential hypertension (EHT). We describe here a polymerase chain reaction-based assay for detection of a BglI dimorphic site located in the first intron of the REN gene. In this retrospective, case-control, association study, we investigated BglI allele and genotype distributions in 554 subjects (280 hypertensives and 274 normotensives) from the United Arab Emirates (UAE) - a genetically homogeneous ethnic population with no history of smoking or alcohol consumption - and in 485 hypercholesterolemic, US Caucasian subjects (250 hypertensives and 235 normotensives). A statistically significant association was found between alleles on which the BglI site is present [BglI(+)] and clinical diagnosis of EHT in the UAE sample group (odds ratio = 2.69, p = 0.0006), and a similar trend was observed in the US group (odds ratio = 1.97, p = 0.01). BglI(+) homozygous status was also investigated in the US group and found to be associated with elevated systolic and diastolic blood pressure values (respectively, 144.8+/-26.1 vs. 134.1+/-23.0 mm Hg, p = 0.04; and 91.0+/-12.5 vs. 82.2+/-12.7 mm Hg, p = 0.009). In conclusion, variations of the REN (or of a nearby) gene that may be in linkage disequilibrium with the REN BglI(+) marker could play a role in contributing to an increased individual's genetic susceptibility to EHT in the UAE population and amongst US hypercholesterolemic Caucasians. Such a genetic influence, which seems to show a recessive mode of inheritance, could also be implicated in raising both systolic and diastolic blood pressures.

Adult↗
PubMed1999

A multilocus genotyping assay for candidate markers of cardiovascular disease risk.

A number of chronic diseases, including cardiovascular disease, appear to have a multifactorial genetic risk component. Consequently, techniques are needed to facilitate evaluation of complex genetic risk factors in large cohorts. We have designed a prototype assay for genotyping a panel of 35 biallelic sites that represent variation within 15 genes from biochemical pathways implicated in the development and progression of cardiovascular disease. Each DNA sample is amplified using two multiplex polymerase chain reactions, and the alleles are genotyped simultaneously using an array of immobilized, sequence-specific oligonucleotide probes. This multilocus assay was applied to two types of cohorts. Population frequencies for the markers were estimated using 496 unrelated individuals from a family-based cohort, and the observed values were consistent with previous reports. Linkage disequilibrium between consecutive pairs of markers within the apoCIII, LPL, and ELAM genes was also estimated. A preliminary analysis of single and pairwise locus associations with severity of atherosclerosis was performed using a composite cohort of 142 individuals for whom quantitative angiography data were available; evaluation of the potentially interesting associations observed will require analysis of an independent and larger cohort. This assay format provides a research tool for studies of multilocus genetic risk factors in large cardiovascular disease cohorts, and for the subsequent development of diagnostic tests.

Adult↗
PubMed1999

Renin gene MboI dimorphism is a discriminator for hypertension in hyperlipidaemic subjects.

As renin is the key enzyme of the renin-angiotensin-aldosterone system, the renin gene (REN) represents a good candidate quantitative trait locus for investigations aimed at uncovering the molecular and genetic influences implicated in the molecular etiology of essential hypertension. Among the various polymorphic markers that are available at the REN gene locus, an MboI dimorphic site located in the ninth intron of the REN gene has previously been shown to be significantly associated with a family history of hypertension in a Japanese population and with direct clinical diagnosis of essential hypertension in a Gulf population. We determined MboI allele and genotype distributions in a sample population of 349 (178 men, 171 women) hyperlipidaemic US Caucasians (mean age 55.4+/-13.1 yr), comprising 122 hypertensive and 227 normotensive subjects. A statistically significant association was found between alleles on which the MboI site was present [MboI(+)] and clinical diagnosis of hypertension. REN MboI(+) alleles are thus in linkage disequilibrium with genetic influences that contribute to increased individual susceptibility to hypertension of hyperlipidaemic patients (with an associated odds ratio of 2.15, 95% CI: 1.34-3.45). This positive association does not seem to occur through the effect of classical risks factors represented by lipid, lipoprotein and apolipoprotein levels.

Adult↗
PubMed1999

The apolipoprotein B R3531C mutation. Characteristics of 24 subjects from 9 kindreds.

Familial ligand-defective apolipoprotein B (apoB) is a group of disorders caused by mutations in the apoB gene. In this report the R3531C mutation is characterized further using a monoclonal antibody MB19/dynamic laser light scattering technique to measure ratios of Cys(3531) to normal low density lipoprotein (LDL) particles. All six subjects studied showed a preferential accumulation of particles carrying the defective apoB allotype. We determined binding properties of LDL from R3531C heterozygotes by measurement of high-affinity binding to LDL receptors on fibroblasts and its ability promote growth of U937 cells. LDL from R3531C heterozygotes, compared to normal LDL, had 49.3% of the binding affinity and was 74% as effective in a U937 cell proliferation assay. To identify new probands, we screened 2570 subjects for the R3531C mutation. Nine probands were found with 15 affected relatives. Of the seven haplotypes we uncovered, two were novel, while five were identical to one initially reported as associated with Cys3531. Three silent mutations were detected also: T3540T, N3542N and T3552T. Analysis of lipid profiles of R3531C families showed, as with the R3500Q mutation, variable expression of the phenotype, modulated by environmental and other genetic factors. Both mutations tend to produce lower plasma levels of LDL in affected subjects than do defects of the LDL receptor (familial hypercholesterolemia, FH). This study shows that the Cys(3531) LDL particles are not only defective at binding to the LDL receptor, as determined by two separate methods, but that in all cases they accumulate preferentially compared to the normal allotype.-Pullinger, C. R., D. Gaffney, M. M. Gutierrez, M. J. Malloy, V. N. Schumaker, C. J. Packard, and J. P. Kane. Apolipoprotein B R3531C mutation: characteristics of 24 subjects from 9 kindreds. .

Adolescent↗
PubMed1998

Endothelial dysfunction occurs in children with two genetic hyperlipidemias: improvement with antioxidant vitamin therapy.

OBJECTIVE: To measure endothelium-dependent vascular relaxation in children with two genetic hyperlipidemias and to assess the effect of antioxidant vitamins on endothelial dysfunction. STUDY DESIGN: Vascular reactivity in the brachial artery was measured in 45 individuals between 6 and 21 years of age (18 with familial hypercholesterolemia [FH], 15 with familial combined hyperlipoproteinemia [FCH], 12 control subjects) with the use of high-resolution two-dimensional ultrasonography. Follow-up studies were done for 11 children after 6 weeks of treatment with tocopherol (400 IU twice a day) and ascorbic acid (500 mg twice a day). RESULTS: The mean percent change in diameter during reactive hyperemia was 2.1 +/- 2.2 (SD) and 2.7 +/- 4.4, in FH and FCH, respectively, compared with 12. +/- 4.9 among control subjects (p < 0.001 in each case). The mean percent dilation was significantly increased (2.8 +/- 1.6 to 9.1 +/- 2.3) (p < 0.001) after antioxidant therapy. CONCLUSIONS: Impaired endothelium-dependent vasoregulation occurs in children with FCH as well as in those with FH. The improvement in vascular reactivity observed during supplementation with antioxidant vitamins suggests that reactive oxygen species derived from oxidized lipoproteins may be responsible for the impairment of vasoregulation in subjects with hyperlipidemia.

Adolescent↗
PubMed1998

A multilocus genotyping assay for cardiovascular disease.

In our efforts to develop diagnostic tests for complex multifactorial disorders, and to assist the research community in evaluating genetic markers for predisposition to cardiovascular disease, we have developed a prototype assay to genotype up to 35 variable sites among 15 genes. The candidate markers in this panel were selected from biological pathways likely to contribute to the development and progression of cardiovascular disease. Each sample is amplified in two multiplex polymerase chain reactions that are then hybridized to an array of immobilized oligonucleotide probes. The assay has been applied to a population-based cohort representing 238 families; allele frequencies observed among 455 unrelated parents from this cohort agree with available literature values. Data from a cohort of 142 lipid-clinic patients were used to explore locus associations with arterial occlusion, as measured by quantitative angiography. This prototype assay provides a research tool for studies to assess the association of multiple markers with disease, and for clinical studies to evaluate marker association with patient responsiveness to experimental therapies.

Adult↗
PubMed1998

Prebeta-1 HDL in plasma of normolipidemic individuals: influences of plasma lipoproteins, age, and gender.

Prebeta-1 HDL is a molecular species of plasma HDL of approximately 67 kDa mass that contains apolipoprotein A-I, phospholipids, and unesterified cholesterol. It participates in a cyclic process involved in the retrieval of cholesterol from peripheral tissues. In this cycle, unesterified cholesterol from cells is incorporated into prebeta-1 HDL, providing a substrate for esterification of cholesterol by lecithin:cholesterol acyltransferase. Prebeta-1 HDL then becomes incorporated into larger HDL species of alpha mobility as esterification proceeds and is regenerated during the transfer of cholesteryl esters from alpha HDL particles to acceptor lipoproteins. Thus the steady state level of prebeta-1 HDL in plasma reflects the relative efficiencies of the major metabolic processes involved in its generation and removal. We have used an isotope dilution technique to measure prebeta-1 HDL levels in the plasmas of 136 normolipidemic individuals (46 M, 90 F). The mean absolute concentration of prebeta-1 HDL as apolipoprotein A-I was 68 +/- 40 microg/ml for women, and 84 +/- 49 m/ml for men. Prebeta-1 HDL represented 5.5 +/- 3.3% of total apolipoprotein A-I in women, and 7.2 +/- 4.0% in men. The distributions of both absolute and percent prebeta-1 HDL are highly asymmetric, with skew toward higher values. However, the skew appears not to be attributable to either plasma cholesterol or triglyceride levels which are also skewed in population samples. The percent prebeta-1 HDL was negatively correlated with HDL cholesterol levels (P < 0.0001), whereas absolute levels of prebeta-1 HDL were positively correlated with apolipoprotein A-I and negatively correlated with HDL cholesterol (P, for both, < 0.0001). Multiple linear regression analysis revealed effects of age and gender, but no association with lipoprotein fractions other than HDL. Lower levels of prebeta-1 HDL were associated with female gender in all models.

Adolescent↗
PubMed1997

Premature coronary artery disease associated with a disruptive mutation in the estrogen receptor gene in a man.

BACKGROUND: While estrogens protect against coronary artery disease in women, it is unclear whether they influence cardiovascular function in men. The present report describes coronary vascular abnormalities and the lipoprotein profile of a male patient with estrogen insensitivity caused by a disruptive mutation in the estrogen-receptor gene. METHODS AND RESULTS: Stress thallium scintigraphy, echocardiography, and electron-beam computed tomography (CT) scanning of the coronary arteries and detailed lipoprotein analysis were performed. Electron-beam CT scanning of the coronary arteries showed calcium in the left anterior descending artery. Lipoprotein analysis showed relatively low levels of total (130 mg/dL), LDL (97 mg/dL), and HDL (34 mg/dL) cholesterol; apolipoprotein A-I (91.7 mg/dL); and lipoprotein(a) (4.1 nmol/L), but normal levels of triglycerides (97 mg/dL) and pre-beta-1-HDL cholesterol (61 microg/mL). CONCLUSIONS: The absence of functional estrogen receptors may be a novel risk factor for coronary artery disease in men.

Adult↗
PubMed1997

Apolipoprotein L, a new human high density lipoprotein apolipoprotein expressed by the pancreas. Identification, cloning, characterization, and plasma distribution of apolipoprotein L.

In this study, we have identified and characterized a new protein present in human high density lipoprotein that we have designated apolipoprotein L. Using a combination of liquid-phase isoelectrophoresis and high resolution two-dimensional gel electrophoresis, apolipoprotein L was identified and partially sequenced from immunoisolated high density lipoprotein (Lp(A-I)). Expression was only detected in the pancreas. The cDNA sequence encoding the full-length protein was cloned using reverse transcription-polymerase chain reaction. The deduced amino acid sequence contains 383 residues, including a typical signal peptide of 12 amino acids. No significant homology was found with known sequences. The plasma protein is a single chain polypeptide with an apparent molecular mass of 42 kDa. Antibodies raised against this protein detected a truncated form with a molecular mass of 39 kDa. Both forms were predominantly associated with immunoaffinity-isolated apoA-I-containing lipoproteins and detected mainly in the density range 1.123 < d < 1.21 g/ml. Free apoL was not detected in plasma. Anti-apoL immunoaffinity chromatography was used to purify apoL-containing lipoproteins (Lp(L)) directly from plasma. Nondenaturing gel electrophoresis of Lp(L) showed two major molecular species with apparent diameters of 12.2-17 and 10.4-12.2 nm. Moreover, Lp(L) exhibited both pre-beta and alpha electromobility. Apolipoproteins A-I, A-II, A-IV, and C-III were also detected in the apoL-containing lipoprotein particles.

Amino Acid Sequence↗
PubMed1997

Measurement of prebeta-1 HDL in human plasma by an ultrafiltration-isotope dilution technique.

Prebeta-1 HDL is a 67-kDa species of plasma high-density lipoproteins (HDL) that contains two copies of apolipoprotein A-I. It functions in a metabolic cycle of cholesterol retrieval and may be formed during lipolysis in plasma. We have found that centrifugal ultrafiltration using a membrane with a permeability limit of 100 kDa discriminates categorically between the 67-kDa species and larger HDL particle species. Thus, the ultrafiltrate samples the pool of prebeta-1 HDL in plasma. We have developed a technique using the dispersal of purified prebeta-1 HDL, labeled covalently with tritium, in plasma samples, to label the prebeta-1 HDL pool. Subsequent determination of the specific activity of prebeta-1 HDL in the ultrafiltrate provides a means of calculating the content of prebeta-1 HDL in plasma by the isotope dilution principle. We employ a modification of an enzyme-linked immunosorbent assay technique for apolipoprotein A-I that allows the equal detection of that protein in prebeta-1 HDL and in other HDL particle species for determination of the fraction of total apolipoprotein A-I that is present in the prebeta-1 HDL particle species. The mean level of prebeta-1 HDL-associated apolipoprotein A-I in plasma samples from 86 normolipidemic adults was 74 +/- 43 microg/ml (+/-SD), representing an average of 6.6% of the total apolipoprotein A-I in plasma.

Adult↗
PubMed1997

A novel apolipoprotein C-III variant, apoC-III(Gln38-->Lys), associated with moderate hypertriglyceridemia in a large kindred of Mexican origin.

Apolipoprotein C-III (apoC-III) is a major protein component of very low density lipoproteins (VLDL), chylomicrons, and a minor component of high density lipoproteins (HDL). Studies of naturally occurring human variants of apoC-III will help in adding to our understanding of the physiological function of this apolipoprotein. Using isoelectric focusing (IEF) of VLDL fractions we screened over 2500 lipid clinic patients and have identified an individual with a novel apoC-III variant. DNA sequencing revealed the variant to be a Lys for GIn exchange at amino acid residue 38 due to an A for C substitution in exon 3. This was confirmed by NH2-terminal protein sequence analysis. The mutant Lys38 variant was present in VLDL at about the same level as the normal form although the total amount of apoC-III was increased by 34%. The proband, a 16-year-old boy of Mexican origin, had a plasma level of total triglycerides above the 95th percentile for his age. Family studies revealed a further 16 individuals who were heterozygous for this apoC-III (Gln38-->Lys) variant. Compared to 21 unaffected relatives, the 17 heterozygous subjects had a statistically significant 32% elevation of their plasma levels of triglycerides when adjusted for age, sex, body mass index, and lifestyle. Other lipid and lipoprotein values were unaffected. The presence of an additional positive charge at residue 38 suggests that this residue is involved in the function of apoC-III. The elevation of plasma levels of triglycerides supports the view that apoC-III is involved in the regulation of the catabolism of triglyceride-rich lipoproteins.

Adolescent↗
PubMed1996

Angiographically silent atherosclerosis detected by intravascular ultrasound in patients with familial hypercholesterolemia and familial combined hyperlipidemia: correlation with high density lipoproteins.

OBJECTIVES: This study sought to evaluate the extent of atherosclerosis in coronary and iliac arteries in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia, using intravascular ultrasound imaging. BACKGROUND: Intravascular ultrasound imaging provides cross-sectional tomographic views of the vessel wall and allows quantitative assessment of atherosclerosis. METHODS: Forty-eight nonsmoking, asymptomatic patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia underwent intravascular ultrasound imaging of the left anterior descending coronary, left main coronary and common iliac arteries. Angiography showed only minimal or no narrowing in these vessels. Intravascular ultrasound images obtained during catheter pullback underwent morphometric analysis. Plaque burden was expressed as the mean and maximal intimal index (ratio of plaque area and area within the internal elastic lamina) and as the percent of vessel surface covered by plaque. RESULTS: Intravascular ultrasound detected plaque more frequently than angiography in the left anterior descending (80% vs. 29%, respectively), left main (44% vs. 16%) and iliac arteries (33% vs. 27%). Plaque burden was higher in the left anterior descending (mean intimal index [+/- SD] 0.25 +/- 0.16) than in the left main (0.11 +/- 0.16, p < 0.001) and iliac arteries (0.02 +/- 0.04, p < 0.001). Angiography detected lumen narrowing only in coronary arteries with a maximal intimal index > or = 0.42 (left anterior descending artery) and > or = 0.43 (left main artery). The area within the internal elastic lamina increased with plaque area in the left anterior descending (r = 0.82, p < 0.001) and left main arteries (r = 0.53, p < 0.001). By stepwise multiple regression analysis, the strongest predictor for plaque burden in the left anterior descending artery was the level of high density lipoprotein (HDL) cholesterol and total/HDL cholesterol ratio for the left main artery. CONCLUSIONS: In patients with heterozygous familial hypercholesterolemia and familial combined hyperlipidemia, extensive coronary plaque is present despite minimal or no angiographic changes. Compensatory vessel enlargement and diffuse involvement with eccentric plaque may account for the lack of angiographic changes. Levels of HDL cholesterol and total/HDL cholesterol ratio are far more powerful predictors of coronary plaque burden than are low density lipoprotein cholesterol levels in these patients with early, asymptomatic disease.

Adult↗
PubMed1996

Effect of cholestyramine resin on single dose valproate pharmacokinetics.

Cholestyramine, a nonabsorbable anion exchange resin, has been reported to bind concomitantly administered drugs and decrease their bioavailability. The objective of the study was to determine the effect of cholestyramine on the plasma concentrations of valproic acid (VPA) following concurrent and staggered (VPA 3 hours before cholestyramine) dosing. Six healthy volunteers participated in an open-label, 3-way crossover study. In each phase fasting subjects received 250 mg of VPA followed by serial blood sampling for VPA plasma concentrations over a 37-hour period. In the concurrent and staggered phase the subjects received 4 g of cholestyramine (CHOL) twice daily 24 hours prior to and following the VPA dose. During the concurrent phase the coadministration of CHOL resulted in a decrease (p < 0.05) in the area under the curve (AUC) for VPA compared to VPA alone (415.2 +/- 113.2 mg*hr/l vs 489.2 +/- 153.0 mg*hr/l, respectively). When the same dose of each drug was administered 3 hours apart, the AUC for VPA (454.8 +/- 123.1 mg*hr/l) was not significantly decreased when compared to VPA alone (489.2 +/- 153.0 mg*hr/l). Also, the bioavailability relative to VPA alone was 86.2% +/- 7.1 for the concurrent phase and 95.3% +/- 13.6 for the staggered phase. Based on the AUC of VPA concurrent administration of CHOL significantly decreases VPA absorption and separating the doses of the 2 drugs by 3 hours may lessen the interaction.

Adolescent↗
PubMed1995

Increased prevalence of coronary ectasia in heterozygous familial hypercholesterolemia.

BACKGROUND: Although coronary atherosclerosis most commonly produces clinical effects as a result of stenosis, aneurysmal disease also occurs. We have found an increased prevalence of ectasia and aneurysmal disease in familial hypercholesterolemia (FH) suggesting a link between plasma lipoproteins and coronary aneurysms. METHODS AND RESULTS: In 197 asymptomatic subjects with FH, we examined the prevalence of ectasia and its association with coronary risk factors. An ectatic segment was defined as one with a luminal diameter > 1.5 times that of the adjacent normal segment, excluding poststenotic dilation. Among subjects with FH, 15% had ectasia compared with 2.5% of an age- and sex-matched control group of 198 subjects without FH presenting for coronary angiography (P < .001). These control patients had significantly more severe coronary atherosclerosis than patients with FH. Ectasia was 3 times more common in men than women (P < .025). Neither age nor hypertension was predictive. Although in part reflecting the striking sex differential, ectasia was strongly associated with a lower HDL cholesterol level (P = .003), a higher LDL/HDL ratio (P = .003), and to a lesser extent, a higher LDL cholesterol level (P = .07). No association was found with plasma triglycerides or very low-density lipoprotein cholesterol levels. Among FH patients, ectasia was strongly associated with an overall index of occlusive atherosclerotic disease, based on quantitative angiography (P = .004). Intracoronary ultrasound interrogation of aneurysmal segments revealed circumferential intimal thickening. CONCLUSIONS: Coronary ectasia is more prevalent in patients with FH than in other patients with coronary atherosclerosis and shows a strong inverse association with HDL cholesterol levels. This suggests that disordered lipoprotein metabolism in FH may predispose patients to aneurysmal coronary artery disease.

Adult↗
PubMed1995

Familial ligand-defective apolipoprotein B. Identification of a new mutation that decreases LDL receptor binding affinity.

Detection of new ligand-defective mutations of apolipoprotein B (apoB) will enable identification of sequences involved in binding to the LDL receptor. Genomic DNA from patients attending a lipid clinic was screened by single-strand conformation polymorphism analysis for novel mutations in the putative LDL receptor-binding domain of apoB-100. A 46-yr-old woman of Celtic and Native American ancestry with primary hypercholesterolemia (total cholesterol [TC] 343 mg/dl; LDL cholesterol [LDL-C] 241 mg/dl) and pronounced peripheral vascular disease was found to be heterozygous for a novel Arg3531-->Cys mutation, caused by a C-->T transition at nucleotide 10800. One unrelated 59-yr-old man of Italian ancestry was found with the same mutation after screening 1,560 individuals. He had coronary heart disease, a TC of 310 mg/dl, and an LDL-C of 212 mg/dl. A total of eight individuals were found with the defect in the families of the two patients. They had an age- and sex-adjusted TC of 240 +/- 14 mg/dl and LDL-C of 169 +/- 10 mg/dl. This compares with eight unaffected family members with age- and sex-adjusted TC of 185 +/- 12 mg/dl and LDL-C of 124 +/- 12 mg/dl. In a dual-label fibroblast binding assay, LDL from the eight subjects with the mutation had an affinity for the LDL receptor that was 63% that of control LDL. LDL from eight unaffected family members had an affinity of 91%. By way of comparison, LDL from six patients heterozygous for the Arg3500-->Gln mutation had an affinity of 36%. The percentage mass ratio of the defective Cys3531 LDL to normal LDL was 59:41, as determined using the mAb MB19 and dynamic laser light scattering. Thus, the defective LDL had accumulated in the plasma of these patients. Using this mass ratio, it was calculated that the defective Cys3531 LDL particles bound with 27% of normal affinity. Deduced haplotypes using 10 apoB gene markers showed the Arg3531-->Cys alleles to be different in the two kindreds and indicates that the mutations arose independently. The Arg3531-->Cys mutation is the second reported cause of familial ligand-defective apoB.

Adult↗