Lipid Composition Of HDL Research Articles

Metabolic and functional relevance of HDL subspecies

Our purpose is to review recent findings highlighting the metabolic and functional diversity of HDL subspecies. HDL heterogeneity - both structural and functional - is the main focus of this review. Recent work indicates that the metabolism and functionality of HDL particles differ greatly among HDL subspecies. With the introduction of new and improved methodology (e.g., proteomics), new aspects of the structural complexity and functionality of HDL have been revealed. It has been confirmed that HDL functions - including, but not limited to decreasing inflammation, apoptosis, macrophage adhesion to the endothelium and insulin resistance - are due to HDL's ability to remove cholesterol from cells (reverse cholesterol transport). A new level of HDL complexity has recently been revealed by investigating the lipid composition of HDL with gas chromatography, gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. There are about 100 different HDL-associated proteins; however, there are many more lipid species potentially associated with HDL particles. The most important recent findings disclose that HDL is more complex than previously thought. HDL subclasses differ in physical-chemical properties, protein and lipid composition, metabolism, physiological functions and pathophysiological significance. The staggering complexity of HDL demands significantly more investigation before we can truly begin to understand HDL metabolism and function in humans.

HDL Composition Regulates Displacement of Cell Surface‐Bound Hepatic Lipase

HDL is able to displace cell surface-bound hepatic lipase (HL) and stimulate vascular triglyceride (TG) hydrolysis, much like heparin. Displacement appears to be a result of a high-affinity association of HL and apoA-I. HDL varies in its ability to displace HL, and therefore experiments were undertaken to evaluate the impact of HDL composition and structure on HL displacement from cell surface proteoglycans. HDL apolipoprotein and lipid composition directly affect HL displacement. ApoA-II and apoC-I significantly increase HL displacement from the cell surface. While changes in HDL cholesteryl ester and fatty acid content have no effect on HL displacement, increases in HDL phospholipid and TG content significantly inhibit HL displacement. HDL fractions from hyperlipidemic patients are unable to displace HL from the cell surface. These results indicate that the structure and composition of HDL particles in plasma are central to regulation of HL displacement and the hydrolytic activity of HL.

High-density lipoprotein subclasses distribution and composition in Mexican adolescents with low HDL cholesterol and/or high triglyceride concentrations, and its association with insulin and c-reactive protein

We tested whether low high-density lipoprotein cholesterol (HDL-C) and/or high triglycerides are associated to abnormal HDL subclasses distribution and composition, and their relationships with fasting insulin and C-reactive protein (CRP). Four groups of adolescents were studied: group 1 (HDL-C ≤ 35 mg/dl + TG ≥ 150 mg/dl; n = 16); group 2 (isolated HDL-C ≤ 35 mg/dl; n = 31); group 3 (isolated TG ≥ 150 mg/dl; n = 20); and group 4 (CT < 200 mg/dl, HDL-C > 35 mg/dl, LDL-C < 130 mg/dl, and TG < 150 mg/dl; n = 39). Tanner score-adjusted proportions of large subspecies (HDL 2b, HDL 2a) were lower, and small (HDL 3b, HDL 3c) were higher in groups 1, 2 and 3 than in group 4. As a result, HDL particle size in the three dyslipidemic groups was smaller than in group 4 ( p < 0.001). HDL CE, FC, PL, and apo AI percent contents were lower, whereas HDL TG percent content was higher in groups 1, 2 and 3 compared to group 4. CRP median values were also significantly higher in the three groups with dyslipidemia than in normolipidemic subjects (group 4). Fasting Insulin concentration and HOMA-IR were significantly higher in group 1 than in the other three groups. In stepwise multivariate analysis HDL subclass distribution and composition were independently associated only with HDL-C and waist circumference. As reported in adults, adolescents with low HDL-C and/or high TG have abnormalities in HDL subclasses distribution and lipid composition, which may render their HDL dysfunctional. In addition, these subjects have high CRP and insulin levels suggesting the presence of chronic low-grade inflammation.

Endothelial lipase is less effective at influencing HDL metabolism in vivo in mice expressing apoA-II

Endothelial lipase (EL) plays an important physiological role in modulating HDL metabolism. Data suggest that plasma contains an inhibitor of EL, and previous studies have suggested that apolipoprotein A-II (apoA-II) inhibits the activity of several enzymes involved in HDL metabolism. Therefore, we hypothesized that apoA-II may reduce the ability of EL to influence HDL metabolism. To test this hypothesis, we determined the effect of EL expression on plasma phospholipase activity and HDL metabolism in human apoA-I and human apoA-I/A-II transgenic mice. Expression of EL in vivo resulted in lower plasma phospholipase activity and significantly less reduction of HDL-cholesterol, phospholipid, and apoA-I levels in apoA-I/A-II double transgenic mice compared with apoA-I single transgenic mice. We conclude that the presence of apoA-II on HDL particles inhibits the ability of EL to influence the metabolism of HDL in vivo.

Effect of hormone replacement therapy on the reverse cholesterol transport

Hormone replacement therapy (HRT) in healthy postmenopausal women modifies the HDL lipid composition, selectively increases the HDL subpopulation that only contains apolipoprotein A-I (LpA-I) and decreases the activity of phospholipid transfer protein (PLTP), a key protein regulating HDL levels. In addition, HRT increases the plasma capacity to promote cholesterol efflux in vitro. These findings demonstrate that HRT not only increases HDL-cholesterol levels, but also modifies HDL physiochemical properties, possibly optimising its function in the reverse cholesterol transport.

Characterization of lipoproteins from the turtle, Trachemys scripta elegans, in fasted and fed states

The lipid and apolipoprotein composition of VLDL, IDL, LDL, HDL 2 and HDL 3 were examined in the turtle, Trachemys scripta elegans, in fasted and fed states. The lipid composition of turtle lipoproteins was very similar to their human counterparts. The major apolipoprotein found in LDL, IDL and VLDL, which has a molecular weight of approximately 550 kD, is a homologue of apoB100. The major apolipoprotein found in both HDL 2 and HDL 3, has a molecular weight of 28-kD and is homologous to human apoA-I. HDL 3 also contains a 6.5 kD protein that is homologous to apoA-II, while HDL 2 has two low molecular weight proteins of 6 kD and 7 kD which are also found on the triglyceride rich lipoproteins (TRL). The 7 kD protein is homologous to apoC-III, while the 6 kD protein has a similar size and distribution as apoC-II or apoC-I. In addition, HDL 2 also possesses a protein of 15.8 kD that has no obvious mammalian homologue. In both size and apolipoprotein composition, turtle HDL 2 resembles human HDL 2b while turtle HDL 3 resembles human HDL 3. In the fasted state, turtles contained very little TRL. When fed a high fat diet, the amount of IDL and LDL sized particles increased significantly.

Analysis of the relationship between triglyceridemia and HDL-phospholipid concentrations: consequences on the efflux capacity of serum in the Fu5AH system

The high triglyceride/low HDL-cholesterol trait is a common finding in the general population. The aim of the present study was to analyze and interpret the relationships between triglycerides (TG), HDL-related parameters and serum cholesterol efflux potential in an asymptomatic population including both normo- and hyperlipidemic individuals. In a large sample ( n=1143) of this population, there was a negative correlation between TG and HDL-cholesterol (HDL-C) ( r=−0.49, P<0.0001) whereas the negative correlation between TG and HDL-phospholipid (HDL-PL) ( r=−0.29, P<0.0001) was weaker, leading to a strong positive correlation between TG and HDL-PL/C ratio ( r=0.58, P<0.0001). Thus, increased TG concentrations were associated with an enrichment of HDL with PL. Since we have demonstrated previously that HDL-PL is the major determinant for cholesterol efflux potential from Fu5AH rat hepatoma cells, we determined the effect of the variations in HDL lipid composition on the cholesterol efflux capacity in a subsample of 198 subjects. Compared with normolipidemic subjects (NLP) (TG≤1.7 mmol/l; LDL-C≤4.1 mmol/l, n=58), hypertriglyceridemic subjects (HTG) (TG>1.7 mmol/l, n=63) exhibited lower HDL-C levels (1.08±0.21 vs. 1.25±0.32, P=0.0003) whereas they showed similar HDL-PL concentrations (1.25±0.21 vs. 1.25±2.7) and, thus, higher HDL-PL/C ratio (1.17±0.15 vs. 1.02±0.14, P=0.0001). The relative efflux capacity of serum measured in the Fu5AH system (5% serum, 4 h incubation at 37°C) was on average identical in the HTG and NLP groups. Thus, this study provides evidence that despite decreased HDL concentrations, as determined routinely by the HDL-C assay, some HTG subjects maintained serum cholesterol efflux capacity thanks to the enrichment of HDL with PL.

Comparative analysis of lipid composition of normal and acute-phase high density lipoproteins

In the acute-phase response and in diseases with prolonged acute phases, normal HDL (NHDL) is converted into acute-phase HDL (APHDL) and becomes proinflammatory and unable to protect LDL against oxidative modification. Earlier work had demonstrated that these changes are associated with alterations in apolipoprotein composition and enzymatic activity of APHDL, but the effect of the acute-phase condition on the lipid composition of APHDL had remained obscure. The present study shows marked quantitative differences in lipid composition between NHDL and APHDL. Specifically, APHDL contained 25% less total lipid per milligram of protein. Up to 50% of cholesteryl ester in the lipid core of APHDL was replaced by triacylglycerol; however, the total phospholipid/total neutral lipid ratios were the same as in NHDL, both lipoproteins giving similar calculated lipid core radii. Furthermore, the phosphatidylcholine/sphingomyelin ratio in APHDL was nearly double that in NHDL, indicating a relative loss of sphingomyelin. A decrease was also seen in diacyl and alkenylacyl glycerophosphatidylethanolamine as well as in phosphatidylinositol of APHDL when compared with NHDL. APHDL contained proportionally more saturated and less polyunsaturated and isoprostane-containing species of phosphatidylcholine, as well as more saturated than unsaturated cholesteryl esters. APHDL also contained significantly more free fatty acids, lysophosphatidylcholine, and free cholesterol.These changes in the lipid composition of HDL are consistent with the alterations in the apoprotein composition and enzymatic activity of APHDL and indicate proinflammatory and proatherogenic roles for APHDL.

Inhibition of cholesteryl ester transfer protein activity in hamsters alters HDL lipid composition

We investigated the role of cholesteryl ester transfer protein (CETP) in hamsters by using a monoclonal antibody (MAb) that inhibited hamster CETP activity. MAbs were prepared against partially purified human CETP and screened for inhibition of 3H-cholesterol oleate (CE) transfer from LDL to HDL in the presence of human plasma bottom fraction ( d > 1.21 g/ml). Antibody 1C4 inhibited CE transfer activity in both human plasma bottom fraction (IC 50 = ∼4 μg/ml) and in whole plasma from male Golden Syrian hamsters (IC 50 = ∼30 μg/ml). Purified MAb I C4 was injected into chow- and cholesterol-fed hamsters, and blood was collected for analysis of plasma CETP activity and HDL lipid composition. Plasma CETP activity was inhibited by 70%–80% at all times up to 24 h following injection of 500 μg MAb 1C4 (∼3.7 mg/kg). The amount of antibody required for 50% inhibition at 24 h post-injection was 200 μg (∼ 1.5 mg/kg). Inhibition of hamster CETP activity in vivo increased hamster HDL cholesterol by 33% ( P < 0.0001), increased HDL-CE by 31% ( P < 0.0001) and decreased HDL-triglyceride by 42% ( P < 0.0001) ( n = 36) as determined following isolation of HDL by ultracentrifugation. An increase in HDL cholesterol and a redistribution of cholesterol to a larger HDL particle were also observed following fast protein liquid chromatography (FPLC) gel filtration of plasma lipoproteins. These results demonstrate that inhibition of CETP activity in hamsters alters HDL lipid composition and particle size and further demonstrate the utility of hamsters as a model for CETP inhibition.

Inhibition of cholesteryl ester transfer protein activity in hamsters alters HDL lipid composition

Inhibition of cholesteryl ester transfer protein activity in hamsters alters HDL lipid composition

Lipoprotein lipases, lipoprotein density gradient profile and LDL receptor activity in miniature pigs fed fish oil and corn oil

The effects of fish oil and corn oil on plasma lipoprotein concentrations, the lipolytic enzymes, lipoprotein lipase and hepatic triacylglycerol lipase, the density distribution of the plasma lipoproteins and LDL receptor activity were studied. These experiments were designed, in part, to define the mechanism(s) responsible for the increased conversion of plasma VLDL apolipoprotein B to LDL and a decreased LDL apolipoprotein B fractional catabolic rate described in previous apolipoprotein B kinetic studies. Miniature pigs were fed diets for 3 to 6 weeks containing supplements of corn oil or fish oil as Maxepa. Triacylglycerol and cholesterol in plasma and VLDL were significantly reduced by the fish oil diet. LDL and HDL cholesterol were not significantly changed. The fish oil diet significantly reduced post-heparin plasma lipoprotein lipase and hepatic triacylglycerol lipase activities, which may be an adaptive response to the low concentration of substrates (triacylglycerol-rich lipoproteins) for these enzymes. No differences were observed in the density of VLDL, LDL or HDL as determined by density gradient ultracentrifugation with the fish oil diet. No major changes in percent lipid composition of VLDL, LDL and HDL were observed. No differences were found with respect to LDL uptake by J774 macrophages. Receptor mediated clearance of LDL in vivo, as assessed by measuring the difference in fractional catabolic rate of native vs. methylated LDL decreased significantly by 17% ( P < 0.032). We conclude that the increased conversion of VLDL apolipoprotein B to LDL in miniature pigs fed fish oil is not related to an increase in lipolytic enzymes or density distribution of VLDL, but may be due in part to a decrease in LDL receptor activity.

Cholesteryl ester transfer activity in lipoprotein lipase deficiency and other primary hypertriglyceridemias

Cholesteryl ester transfer protein (CETP) activity was measured in d > 1.21 g/ml plasma from hypertriglyceridemic patients and compared with normolipidemic subjects. The assay consisted in measuring the specific transfer of [ 3H]cholesteryl oleate from a prelabelled, apo E-poor HDL fraction to VLDL after incubation at 37°C in the presence of the d > 1.21 g/ml plasma sample: the lipoproteins were then separated by precipitation with dextran sulfate/Mg 2+ solution. Increasing the volume of d > 1.21 g/ml plasma or purified human CETP in the assay produced linear responses in measured activity, whereas, either during incubation at 4°C or in the presence of rat plasma instead of human plasma, the transfer of [ 3H]cholesteryl oleate to VLDL was not stimulated. Thus, the assay reflects changes in CETP in the sample and appears to be suitable for measuring CETP activity in d > 1.21 g/ml plasma. CETP activity was very similar in the two groups of normolipidemic subjects considered: adolescents (203 ± 11 nmol esterified cholesterol transferred per 8 h/ml plasma) and adults (215 ± 5). Patients were grouped into lipoprotein-lipase (LPL)-deficient and non-LPL-deficient according to their enzyme activity in postheparin plasma. CETP activity was highly increased in LPL-deficient, severe hyperchylomicronemic patients (430 ± 42) and was directly correlated with VLDL levels in the non-LPL-deficient individuals. Marked differences were observed in the lipid composition of HDL and apolipoprotein A-I levels among patients and controls. In the control group, CETP activity was correlated only with HDL-triglyceride and HDL-triglyceride/apo A-I mass ratio, which is compatible with the physiological role of CETP in transferring triglyceride to HDL from other lipoprotein particles. When all hypertriglyceridemic patients were considered together, CETP activity was inversely correlated with apo A-I and HDL-cholesterol, whereas it was directly correlated with HDL-triglyceride/HDL-cholesterol and HDL-triglyceride/apo A–I mass ratios. The results indicate that the enhanced CETP activity associated with hypertriglyceridemia contributes to the compositional change of HDL, which in turn may be responsible for the reduction of HDL levels in this condition.

Effects of doxazosin, an α1-adrenergic inhibitor, on plasma lipid and lipoprotein levels, low density lipoprotein metabolism and cholesterol absorption in cynomolgus monkeys

The mechanism(s) by which doxazosin, an a, inhibitor, regulates plasma low density lipoprotein cholesterol (LDLC) and apolipoprotein B (apo B) levels were investigated in ‘normocholesterolemic’ (average total cholesterol (TC) of 218 mg/dl) and ‘hypercholesterolemic’ (average TC of 350 mg/dl) cynomolgus monkeys. Twelve weeks of doxazosin treatment (1 mg/kg per day) significantly reduced plasma TC and LDL-C levels in both groups while high density lipoprotein cholesterol and apolipoprotein A-I concentrations rose. Despite these changes in plasma lipids, LDL and HDL lipid composition was not affected by doxazosin. The reduction in LDL-C and apo B in the doxazosin-treated ‘hypercholesterolemic’ group was associated with a significant increase in both receptor-dependent and -independent LDL apo B fractional catabolic rates. Similar associations were noted in the ‘normocholesterolemic’ group. LDL apo B production or transport rate was not affected by doxazosin. Cholesterol absorption was also significantly reduced by doxazosin which may also contribute to lowering plasma LDL-C levels. These studies suggest that doxazosin treatment can produce beneficial changes in the plasma lipid profile over a wide rage of plasma cholesterol levels by up-regulating LDL fractional clearance.

Interindividual variation in the partition of lipoprotein(a) into lipoprotein subfractions

In order to evaluate cardiovascular risk, we analyzed the lipid composition of HDL and the presence of lipoprotein(a) [Lp(a)] by both agarose gel electrophoresis and enzyme-linked immunoassay (ELISA). In 681 plasmas we found a close correspondence between the existence of a visible sinking pre-β lipoprotein band and a concentration of Lp(a) higher than 300 mg/L. In the sinking pre-β(+) samples, the HDL-cholesterol level obtained by differential ultracentrifugation was significantly higher than that obtained by precipitation with the MgCl 2-phosphotungstic acid reagent; and the difference between these HDL-cholesterol values was linearly correlated with plasma Lp(a) concentration. Moreover, the other HDL lipid components and the lipid mass ratios of HDL lipid components and the lipid mass ratios of HDL isolated by ultracentrifugation were significantly different from those of HDL isolated by precipitation, and these changes were also correlated with plasma Lp(a). These differences are attributed to Lp(a) because it was detected in the 1.063–1.21 kg/L plasma fractions, whereas it was absent in the plasma supernates after precipitation with MgCl 2-phosphotungstic Although to a lesser extent, Lp(a) was also present in the LDL and VLDL density ranges and it directly depended on both the Lp(a) and the triglyceride plasma concentrations. The proportion of Lp(a) in HDL as related to that in LDL density fractions decreased as Lp9a) plasma levels increased, reflecting an interindividual variation of Lp(a) density species. Since 90% of our study population had detectable Lp(a) in plasma, the results reinforce the concept that the ultracentrifugation method is not equivalent to precipitation in most samples, and the contaminant effect of Lp(a) cannot be predicted because of Lp(a) partition into the different lipoprotein fractions.

Metabolic and genetic control of HDL cholesterol levels.

Variation of HDL cholesterol levels in man shows a strong inverse relationship to the incidence of atherosclerotic vascular disease. Thus the regulation of HDL cholesterol levels has been the subject of intense investigation. Human genetic differences in cholesteryl ester transfer protein and hepatic lipase illustrate the importance of these factors in the normal catabolism of HDL, while metabolic and population studies show that lipoprotein lipase activity plays a central role in the transfer of lipids and apoproteins into HDL. Metabolic turnover studies in humans suggest that variations in the fractional catabolism of the HDL structural proteins, apoA-I and apoA-II, account for much of the variation of HDL levels in human populations. Although the catabolism of these apolipoproteins is poorly understood, changes in the core lipid composition of HDL may lead to changes in catabolism of the HDL proteins. The core lipid composition of HDL appears to be determined by lipid transfer processes, and the activities of lipoprotein and hepatic lipase. Thus many genetic and environmental factors that influence HDL levels appear to operate by changing the activities of the lipases or the lipid transfer process.

Changes in serum lipids in rats treated with PGF2a

Serum lipid concentrations were determined in rats treated with PGF2 alpha, PGE1, and controls. Administration of PGF2 alpha in rats influenced only the HDL lipid composition. HDL-cholesterol decreased while HDL-triglycerides increased. No significant difference was observed in the levels of serum total cholesterol, triglycerides, and phospholipids between animals treated with PGF2 alpha and controls. Reduced concentrations of serum lipid levels and especially of HDL-cholesterol, HDL-triglycerides, and HDL-phospholipids were found in the rats treated with PGE1. These results suggest that PGF2 alpha and PGE1 could modify serum lipid levels influencing lipoprotein metabolism.

Interactions of serum proteins with small unilamellar liposomes composed of dioleoylphosphatidylethanolamine and oleic acid: high-density lipoprotein, apolipoprotein A1, and amphipathic peptides stabilize liposomes

Small unilamellar liposomes composed to dioleoylphosphatidylethanolamine (DOPE) and oleic acid (OA) are stabilized by incubation with normal human serum or plasma [Liu, D., & Huang, L. (1989) Biochemistry 28, 7700-7707]. The present report describes a systematic study of interactions of purified serum proteins and lipoproteins with these liposomes. Albumin destabilized liposomes by extracting OA from the liposomes, whereas immunoglobulins and lipoproteins (HDL, LDL, and VLDL) had no effect. However, HDL and, to some extent, VLDL showed a rapid stabilization activity against the lytic effect of albumin. HDL added together with or shortly after the addition of albumin completely abolished the liposome leakage and aggregation effects induced by albumin. SDS-PAGE analysis of the HDL-stabilized liposomes revealed that apolipoprotein A1 was associated with liposomes. Purified apolipoprotein A1, but not a lipid mixture resembling the lipid composition of HDL, showed comparable liposome stabilization activity as HDL. Furthermore, synthetic peptides resembling the amphipathic helices found in apolipoprotein A1 also showed strong liposome stabilization activity. Peptides which were able to form amphipathic helixes of a wedge shape were more effective stabilizers than those which could not. These data indicate that HDL plays a major role in human serum or plasma for the liposome stabilization activity. HDL exerts its activity probably by the interactions of the amphipathic helices of apolipoprotein A1 with the hydrophobic voids found on the outer surface of the highly curved, small liposomes.

原発性高脂血症例のリポ蛋白に関する研究

In this study, phospholipid composition as well as lipid composition of VLDL, LDL and HDL in hypertriglyceridemia and hypercholesterolemia were investigated. As hypercholesterolemic subjects, familial hypercholesterolemia were studied. Lipid composition and phospholipid composition were determined by thin layer chromatography. All hyperlipoproteinemic subjects were classified into type IIa, IIb and IV. In the type ha hyperlipoproteinemia, VLDL has more amounts of cholesterol esters and HDL contains more amounts of free cholesterol than those in the control subjects. In the type IIb hyperlipoproteinemia, VLDL is enriched in free cholesterol. In the type IV hyperlipoproteinemia, LDL and HDL are characterized by an elevation of triglyceride. As for phospholipid, in the type IV, LDL is enriched in phosphatidylcholine (PC) and poor in sphyngomyelin (SM) although other lipoproteins are almost the same composition as those in the control subjects. In the type IIa hypercholesterolemia, compositional change of increment of SM and depletion of PC were observed only in HDL. There was not any change in the type IIb lipoproteins.Furthermore, the data suggest that LDL particle is smaller in type IIa, IIb and IV than normal LDL particle. And HDL particle in familial hypercholesterolemia seems to be less fluid.

Changes of HDL-lipid composition as related to Δ 9-THC action

An attempt was made to investigate the possible action of Δ 9-THC on HDL-Lipid composition. Significant changes were observed in the serum total lipids, triglycerides and HDL subfractions after hashish smoking. The results are discussed in relation to the possible alterations of some enzymatic mechanisms regulating lipid metabolism in hashish users.

A pedigree of homozygous familial hyperalphalipoproteinemia

A new form of familial lipoprotein disorder, homozygous hyperalphalipoproteinemia (HALP) was studied in one pedigree through three generations. The proband was a healthy male, 50 years old, who was checked for a distinctive elevation of plasma high-density lipoprotein cholesterol (HDL-C) in a routine screening examination. An intensive family study revealed that the proband and one of his sisters were homozygotic carriers of familal HALP judging by their extremely high concentration of HDL-C (181 mg/dL and 163 mg/dL, respectively). In the homozygotes, the lipid composition of HDL was found to be normal while the ratio of HDL lipids to apoproteins A-I and A-II tended to be increased. All five children of the two homozygous individuals and two additional first degree relatives were considered to be heterozygous, since their HDL-C values were moderatey elevated, with other lipid levels being normal. The family study thus substantiated the hypothesis, as Glueck et al insisted in 1975, that this lipoprotein disorder is inherited by autosomal dominant transmission. Longevity analysis revealed that the decreased family members showed life prolongation of 9.8 years on an average compared with the appropriate control population of the same district. Our report might be the first to demonstrate the homozygous form of this longevity syndrome.