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Haruyoshi Yoshida

Publications and source records attributed to Haruyoshi Yoshida.

At least 19 recordsLinked to original sources
PubMed2006

Association between trait anxiety and endothelial function observed in elderly males but not in young males.

BACKGROUND AND OBJECTIVES: Endothelial function plays a key role in determining the clinical manifestations of atherosclerosis. Recent reports have shown that healthy elderly subjects with higher trait anxiety tend to have heightened risks of atherosclerotic lesions and cardiovascular disease. The present study was intended to examine whether an association exists between trait anxiety and endothelial function in healthy young and elderly subjects. METHODS: This study examined 26 young male and 30 elderly male subjects using brachial artery flow-mediated dilation (FMD) - a non-invasive ultrasound method - to evaluate endothelial function by measuring the dilation responses of vascular smooth muscle to the nitric oxide produced by endothelial cells following hyperemia. RESULTS: A significant negative correlation was observed between the State and Trait Anxiety Inventory (STAI)-trait score as a parameter of anxiety and the percentage change of FMD (%FMD) in the elderly subjects, but not in the young subjects. The elderly subjects showed significantly lower %FMD than the young subjects. CONCLUSION: These results suggest the possibility that trait anxiety is a predisposing risk factor for cardiovascular damage that might, over a long period, induce atherosclerotic lesions.

Adult↗
PubMed2006

Multifractal analysis of deep white matter microstructural changes on MRI in relation to early-stage atherosclerosis.

Multifractal analysis based on generalized concepts of fractals has been applied to evaluate biological tissues composed of complex structures. This type of analysis can provide a precise quantitative description of a broad range of heterogeneous phenomena. Previously, we applied multifractal analysis to describe heterogeneity in white matter signal fluctuation on T2-weighted MR images as a new method of texture analysis and established Deltaalpha as the most suitable index for evaluating white matter structural complexity (Takahashi et al. J. Neurol. Sci., 2004; 225: 33-37). Considerable evidence suggests that pathophysiological processes occurring in deep white matter regions may be partly responsible for cognitive deterioration and dementia in elderly subjects. We carried out a multifractal analysis in a group of 36 healthy elderly subjects who showed no evidence of atherosclerotic risk factors to examine the microstructural changes of the deep white matter on T2-weighted MR images. We also performed conventional texture analysis, i.e., determined the standard deviation of signal intensity divided by mean signal intensity (SD/MSI) for comparison with multifractal analysis. Next, we examined the association between the findings of these two types of texture analysis and the ultrasonographically measured intima-media thickness (IMT) of the carotid arteries, a reliable indicator of early carotid atherosclerosis. The severity of carotid IMT was positively associated with Deltaalpha in the deep white matter region. In addition, this association remained significant after excluding 12 subjects with visually detectable deep white matter hyperintensities on MR images. However, there was no significant association between the severity of carotid IMT and SD/MSI. These results indicate the potential usefulness of applying multifractal analysis to conventional MR images as a new approach to detect the microstructural changes of apparently normal white matter during the early stages of atherosclerosis.

Aged↗
PubMed2006

Urinary creatinine excretion and protein/creatinine ratios vary by body size and gender in children.

Urinary protein/creatinine ratio (Up/cr) is a simple measurement for evaluation of proteinuria. However, exact effects of body size and gender on urinary excretion of creatinine and Up/cr remain unknown. We aimed to clarify their effects. Early morning urine samples were collected from 124 children with urinary tract disorders. Urinary hourly excretion of creatinine, Ucr (in milligrams per hour), urinary hourly excretion of protein per body surface area, Up (milligrams per square meter per hour), and Up/cr (milligrams per milligram) were calculated. Effects of gender, age, body height, body weight and body surface area on Ucr and Up/cr were analyzed, respectively, in a multiple linear regression model. Body surface area and gender affected Ucr (r2=0.842, P<0.0001). Ucr adjusted by body surface area increased as body surface area grew with moderate variation. Up/cr showed a close correlation with Up and was affected by body height and gender as well. The regression equation showed that Up/cr values corresponding to the normal upper limit of Up, i.e., 4 mg/m2/h, in boys and girls 170 cm tall were approximately one third of those in children 80 cm tall (0.121 vs 0.043 for boys, 0.132 vs 0.047 for girls). The present study indicates that estimation of Up/cr needs to include consideration of children's body height and gender.

Adolescent↗
PubMed2006

Interactions among higher trait anxiety, sympathetic activity, and endothelial function in the elderly.

Negative psychological characteristics have been recognized as independent risk factors of cardiovascular disease (CVD). The purpose of this study was to evaluate the influence of depression and anxiety on cardiac autonomic function and endothelial function in healthy elderly subjects. Forty-six healthy elderly volunteers (mean age 60.8 years) were enrolled in this study. Cardiac autonomic function was assessed by spectral analysis of heart rate variability (HRV) with the head-up tilt test. Brachial artery endothelium-dependent flow-mediated dilation (FMD) was measured using high-resolution ultrasound. A significant positive correlation was observed between the State and Trait Anxiety Inventory (STAI)-trait score as a parameter of anxiety and HRV sympathetic modulation in the supine position (baseline), and a significant negative correlation between this score and the head-up-induced HRV sympathetic response from the baseline. The STAI-trait score also showed a significant negative correlation with the percent change of FMD (%FMD). Analysis using structural equation modeling showed that higher trait anxiety reduced %FMD via abnormalities of sympathetic activity. On the other hand, psychometric parameters of depression were not associated with any HRV component or %FMD. These results suggest that there are specific interactions among higher trait anxiety, abnormalities of sympathetic activity, and endothelial dysfunction. This finding may be useful in clarifying the pathophysiological mechanism by which anxiety is associated with increased risks for atherosclerosis and CVD.

Aged↗
PubMed2006

Correlations of tissue macrophages and cytoskeletal protein expression with renal fibrosis in patients with diabetes mellitus.

BACKGROUND: In clinicopathological studies of cellular remodeling in the progression of diabetic nephropathy, it has not been well described whether tissue macrophage numbers and the expression of two cytoskeletal proteins--alpha-smooth muscle actin (alphaSMA) and vimentin--correlate with the disease severity. METHODS: Renal biopsy specimens from 23 patients with noninsulin-dependent diabetes mellitus (NIDDM) were examined by immunoperoxidase methods for CD68+ macrophages and alphaSMA and vimentin staining in paraffin-embedded samples. alphaSMA staining was evaluated in mesangial and interstitial myofibroblastic cells, and vimentin staining was evaluated in podocytes and mesangial and tubular cells. RESULTS: Glomerular macrophage numbers were not correlated with any clinicopathological scores. However, the interstitial macrophage score was significantly correlated with serum creatinine (sCr) and strongly correlated with the interstitial fibrosis score. Both alphaSMA and vimentin were detectable in the mesangium, without significant correlation with each other. A positive correlation was observed between mesangial alphaSMA and urinary (u-) protein levels. In contrast, an inverse correlation was observed between levels of mesangial vimentin and u-protein. Mesangial alphaSMA, but not vimentin, showed a significant correlation with glomerular sclerosis. Podocytic vimentin levels tended to decrease in patients with higher sCr levels. The severity of interstitial peritubular alphaSMA was correlated strongly with interstitial macrophage proliferation and significantly with the interstitial fibrosis score. CONCLUSIONS: The expression of mesangial alphaSMA may play a role in the progression of glomerular damage, while, on the other hand, newly acquired mesangial vimentin seems to be attenuated by heavy proteinuria. In addition, it was suggested that peritubular alphaSMA-positive myofibroblastic cells, in collaboration with interstitial macrophages, contribute to the progression of interstitial fibrosis in diabetic nephropathy.

Actins↗
PubMed2006

White coat phenomenon, anxiety and endothelial function in healthy normotensive elderly subjects.

OBJECTIVE: The white coat phenomenon (WCP) is a blood pressure (BP) elevation specifically observed in the clinical setting. Though WCP has been suggested to associate with emotional responses such as anxiety or with cardiovascular complications, its pathogenesis and clinical significance are unclear. We studied the possible association between WCP and anxiety or vascular function in normotensive elderly subjects without major cardiovascular risk factors. METHODS: As a parameter of anxiety, the State and Trait Anxiety Inventory (STAI) was used. WCP was evaluated by calculating the difference between the clinic BP and mean daytime ambulatory BP. As parameters of vascular function, brachial artery endothelium-dependent flow-mediated dilation (FMD) and the endothelium-independent dilation response to sublingual glyceryl trinitrate (GTN) were measured using high-resolution ultrasound. RESULTS: Using confounding factors as covariates, no association was observed between WCP and the STAI-trait or STAI-state score. There was a significant negative association between WCP and the percent change of FMD but no association between WCP and the percent change of GTN. CONCLUSION: WCP in the healthy normotensive elderly subjects may reflect a decrease in endothelial function, i.e. initial stage atherosclerosis, rather than anxiety.

Aged↗
PubMed2006

Synthetic/secreting and apoptotic phenotypes in renal biopsy tissues from hypertensive nephrosclerosis patients.

The major glomerular abnormalities in hypertensive nephrosclerosis are described as glomerular obsolescence (GO), glomerulosclerosis (GS), and glomerular collapse (GC). However, glomerular cellular changes caused by hypertensive insults have not been well analyzed. Using an immunoenzyme method, we examined eleven biopsy samples from patients with hypertensive nephrosclerosis for two synthetic and secreting phenotypes, a-smooth muscle actin (alpha-SMA) and collagen type III (Col. III), and two apoptotic phenotypes, pro-apoptotic molecule Bax and anti-apoptotic molecule BcI-2. Together with the glomerular and vascular changes and interstitial fibrosis (IF) area, the results were scored quantitatively and semi-quantitatively and compared to the clinical findings, which included systolic blood pressure (SBP), mean arterial pressure (MAP), serum creatinine levels (sCr) and creatinine clearance (Ccr), using univariate and multivariate analyses. As a result, GS was frequently observed in the mild-to-moderate hypertensive group (140 < or = SBP<180 mmHg), whereas GC was positively correlated with SBP. Furthermore, there was a positive correlation of GS with mesangial alpha-SMA and Col. III, suggesting that GS was the reflection of these synthetic and secreting phenotypic changes in mesangial cells. Endothelial Bax was positively correlated with Ccr (p<0.01); in contrast, podocytic Bax was positively correlated with sCr (p<0.05) and showed a tendency to correlate with MAP (p=0.054). In conclusion, these findings support the view that mesangial synthetic and secreting phenotypic changes may be a reflection of cellular activation caused by mild-to-moderate hypertension and that apoptotic phenotypic expression in podocytes, rather than endothelial cells, may be related to the development of a severe form of hypertensive nephrosclerosis.

Actins↗
PubMed2006

[Changes in autonomic function and EEG power during mental arithmetic task and their mutual relationship].

Meditation is a specific consciousness state in which deep relaxation and increased internalized attention coexist. Autonomic nervous activity during meditation was reported to be characterized by decreased sympathetic activity and increased parasympathetic activity. And concerning EEG power, slow alpha power and fast theta power increased during meditation. On the other hand, mental arithmetic (MA) tasks have been reported to induce an increase in blood pressure and heart rate with enhanced sympathetic activity. However, changes in autonomic nervous activity and EEG power during MA tasks and their mutual relationship have not been adequately studied. In the present study, we quantitatively analyzed the changes in autonomic nervous activity using heart rate variability (HRV) and EEG power during MA task in 30 healthy volunteers. MA task induced significant increases in normalized LF, LF/HF ratio (as a sympathetic index), and a decrease in normalized HF (as a parasympathetic index). On the other hand, significant decrease in EEG power (slow theta: 4-6 Hz and fast alpha: 10-13 Hz in the posterior region and fast theta: 6-8 Hz and slow alpha: 8-10 Hz in all the regions) were induced by MA task. Further evaluation of these changes showed a negative correlation between the change rates (with the control resting condition as the baseline) in fast alpha power and that in LF/HF. These results suggest that specific correlated relationships exist between the change in autonomic nervous activity and EEG power depending on the difference in mental task (i.e., meditation or MA).

Adult↗
PubMed2005

Hypoxia reduces constitutive and TNF-alpha-induced expression of monocyte chemoattractant protein-1 in human proximal renal tubular cells.

Chronic hypoxia has been reported to be associated with macrophage infiltration in progressive forms of kidney disease. Here, we investigated the regulatory effects of hypoxia on constitutive and TNF-alpha-stimulated expression of monocyte chemoattractant protein-1 (MCP-1) in cultured human proximal renal tubular cells (HPTECs). Hypoxia reduced constitutive MCP-1 expression at the mRNA and protein levels in a time-dependent fashion for up to 48 h. Hypoxia also inhibited MCP-1 up-regulation by TNF-alpha. Treatment with actinomycin D showed that hypoxic down-regulation of MCP-1 expression resulted mainly from a decrease in the transcription but not the mRNA stability. Immunoblot and immunofluorescence analyses revealed that treatment with hypoxia or an iron chelator, desferrioxamine, induced nuclear accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) in HPTECs. Desferrioxamine mimicked hypoxia in the reduction of MCP-1 expression. However, overexpression of a dominant negative form of HIF-1alpha did not abolish the hypoxia-induced reduction of MCP-1 expression in HPTECs. These results suggest that hypoxia is an important negative regulator of monocyte chemotaxis to the renal inflamed interstitium, by reducing MCP-1 expression partly via hypoxia-activated signals other than the HIF-1 pathway.

Cell Hypoxia↗
PubMed2005

Changes in EEG and autonomic nervous activity during meditation and their association with personality traits.

Meditation is the attainment of a restful yet fully alert physical and mental state practiced by many as a self-regulatory approach to emotion management, but the psychophysiological properties and personality traits that characterize this meditative state have not been adequately studied. We quantitatively analyzed changes in psychophysiological parameters during Zen meditation in 20 normal adults, and evaluated the results in association with personality traits assessed by Cloninger's Temperament and Character Inventory (TCI). During meditation, increases were observed in fast theta power and slow alpha power on EEG predominantly in the frontal area, whereas an increase in the normalized unit of high-frequency (nuHF) power (as a parasympathetic index) and decreases in the normalized unit of low-frequency (nuLF) power and LF/HF (as sympathetic indices) were observed through analyses of heart rate variability. We analyzed the possible correlations among these changes in terms of the percent change during meditation using the control condition as the baseline. The percent change in slow alpha EEG power in the frontal area, reflecting enhanced internalized attention, was negatively correlated with that in nuLF as well as in LF/HF and was positively correlated with the novelty seeking score (which has been suggested to be associated with dopaminergic activity). The percent change in fast theta power in the frontal area, reflecting enhanced mindfulness, was positively correlated with that in nuHF and also with the harm avoidance score (which has been suggested to be associated with serotonergic activity). These results suggest that internalized attention and mindfulness as two major core factors of behaviors of mind during meditation are characterized by different combinations of psychophysiological properties and personality traits.

Adult↗
PubMed2005

Synergistic effect of hypoxia and TNF-alpha on production of PAI-1 in human proximal renal tubular cells.

BACKGROUND: Chronic hypoxia has been newly proposed as a common mechanism of tubulointerstitial fibrosis in the progression of various chronic inflammatory renal diseases, where plasminogen activator inhibitor-1 (PAI-1) plays an important role in the accumulation of extracellular matrix (ECM) through inhibition of plasmin-dependent ECM degradation. In the present study, we investigated the presence of PAI-1 in renal tubular cells by immunostaining renal biopsy samples. We also closely examined the effects of hypoxia and tumor necrosis factor-alpha (TNF-alpha) on PAI-1 expression in cultured human proximal renal tubular cells (HPTECs). METHODS: Confluent cells growth-arrested in Dulbecco's modified Eagle's medium (DMEM) for 24 hours were exposed to hypoxia (1% O(2)) and/or TNF-alpha at 10 ng/mL for up to 48 hours. Amounts of PAI-1 protein and mRNA after stimulation were measured by enzyme-linked immunosorbent assay (ELISA) and TaqMan quantitative polymerase chain reaction (PCR) or cDNA array analysis, respectively, and compared to those in cells incubated under control conditions (18% O(2) without TNF-alpha). Hypoxia-inducible factor-1alpha (HIF-1alpha) was demonstrated by immunoblot and immunofluorescence analyses. Human PAI-1 promoter activity was estimated by luciferase reporter gene assay. RESULTS: In crescentic glomerulonephritis, clusters of proximal tubules were specifically stained for PAI-1. cDNA array analysis identified PAI-1 as a major gene highly induced by hypoxia in HPTECs. Treatment of 24 hours with hypoxia, TNF-alpha, and their combination induced a 2.8-fold, a 1.8-fold, and a 4.6-fold increase in PAI-1 protein secretion, and produced a 3.6-fold, a 3.3-fold, and a 12.1-fold increase at the PAI-1 mRNA level, respectively. Immunoblot analysis and immunocytochemistry revealed that hypoxia-inducible factor-1alpha (HIF-1alpha) was markedly accumulated in the cell lysates and exclusively translocated to nuclei after 16 hours' exposure of HPTECs to hypoxia but not to TNF-alpha. Luciferase reporter gene assay showed that hypoxia, TNF-alpha, and their combination increased PAI-1 transcription activity by 1.8-fold, 1.4-fold, and 2.2-fold, respectively. A dominant-negative form of HIF-1alpha significantly suppressed PAI-1 transcription activity induced by hypoxia. Inhibition of nuclear factor-kappaB (NF-kappaB) caused a moderate decrease in PAI-1 production under hypoxia. CONCLUSION: Hypoxia induces PAI-1 expression via remarkable nuclear accumulation of HIF-1alpha and partially via NF-kappaB activation in HPTECs. TNF-alpha can synergistically enhance this hypoxia-induced PAI-1 expression.

Antineoplastic Agents↗
PubMed2005

Chromosomal mapping of hyperserum IgA and glomerular IgA deposition in a high IgA (HIGA) strain of DdY mice.

BACKGROUND: The high IgA (HIGA) strain of ddY mice is an inbred model of IgA nephropathy (IgAN), established by selective mating of outbred ddY mice. HIGA mice show high levels of serum IgA and glomerulonephritis with mesangial IgA deposition. To identify the genetic loci responsible for hyperserum IgA and glomerular IgA deposition in this strain, quantitative trait loci analysis was carried out. METHODS: By crossing HIGA with BALB/c mice, 244 F2 generations were produced. Serum IgA levels and glomerular IgA deposition were examined at 40 weeks of age. Genetic markers were typed at 105 microsatellites and the quantitative trait loci of hyperserum IgA and glomerular IgA deposition were confirmed using Map Manager QTX software. RESULTS: Two significant quantitative trait loci of hyperserum IgA were identified on chromosome 2 [logarithm of odds (LOD) = 5.01] and chromsome 4 (LOD = 4.45), and a suggestive quantitative trait locus of hyperserum IgA was located on chromosome 1 (LOD = 3.49). On chromosome 15, a significant quantitative trait locus of glomerular IgA deposition was identified (LOD = 4.40) without the hyperserum IgA locus. Serum IgA level was weakly correlated with the intensity of glomerular IgA in 244 F2 mice; however, the quantitative trait loci of hyperserum IgA were not significantly associated with glomerular IgA deposition. CONCLUSION: These findings indicate that, in HIGA mice, glomerular IgA deposition is mainly regulated by a quantitative trait locus on chromosome 15, and hyperserum IgA synergistically but weakly affect glomerular IgA deposition. The immune disturbance similar to IgAN was revealed to be under multigenic control in HIGA mice.

Animals↗
PubMed2005

[Effects of hypoxia and tumor necrosis factor-alpha on production of plasminogen activator inhibitor-1 in human proximal renal tubular cells].

Chronic hypoxia has been newly proposed as a common mechanism of tubulointerstitial fibrosis in the progression of various chronic inflammatory renal diseases, where PAI-1 plays an important role in the accumulation of extracellular matrix (ECM) through inhibition of plasmin-dependent ECM degradation. In the present study, we investigated the presence of PAI-1 in renal tubular cells by immunostaining renal biopsy samples. We also closely examined the effects of hypoxia and TNF-alpha on PAI-1 expression in cultured human proximal renal tubular cells (HRCs). Confluent cells growth-arrested in DMEM for 24h were exposed to hypoxia (1% O2) and/or TNF-alpha at 10 ng/ml for 24 hours. Amounts of PAI-1 protein and mRNA after stimulation were measured by ELISA and TaqMan quantitative PCR, respectively and compared to those in cells incubated under control conditions (18% O2 without TNF-alpha). HIF-1alpha was demonstrated by immunoblot analysis. In crescentic glomerulonephritis, clusters of proximal tubules were specifically stained for PAI-1. Treatment of 24 hours with hypoxia, TNF-alpha and their combination induced a 2.7-fold, a 1.8-fold, and a 4.6-fold increase in PAI-1 protein secretion, and produced a 3.6-fold, a 3.3-fold, and a 12.1-fold increase at the PAI-1 mRNA level, respectively. Immunoblot analysis revealed that hypoxia-inducible factor-1alpha (HIF-1alpha) was markedly accumulated in the nuclear fraction after 16-hours exposure of HPTECs to hypoxia but not to TNF-alpha. In conclusion, hypoxia induces PAI-1 expression via remarkable nuclear accumulation of HIF-1alpha in HRCs. TNF-alpha can enhance this hypoxia-induced PAI-1 expression.

Cells, Cultured↗
PubMed2004

Quantitative trait loci (QTL) analysis reveals a close linkage between the hinge region and trimeric IgA dominancy in a high IgA strain (HIGA) of ddY mice.

Polymerization of IgA has been suggested as one of the causes of mesangial deposition in IgA nephropathy. HIGA mice are an inbred model of IgA nephropathy, established by selective mating of ddY mice. This strain is characterized by a unique profile of the IgA molecule that is dominantly polymeric and has high serum levels with intense IgA deposition on the mesangium. We carried out quantitative trait loci (QTL) analysis, using F2 generations by crossing HIGA with BALB/c mice. Significant linkage of polymeric IgA in serum samples was identified around D12Mit263, which is close to the gene of the immunoglobulin heavy chain on chromosome 12. The amino acid sequence of the alpha heavy chain revealed marked differences between BALB/c and HIGA mice. Furthermore, most differences were focussed on the hinge region. The DBA/2J strain, which has the same amino acid sequence in the hinge region as the HIGA strain, also showed polymeric IgA dominance but low IgA levels in sera. Size fraction analysis revealed that these polymeric IgA showed trimer dominance in both DBA/2J and HIGA mice. In conclusion, the hinge region plays a key role in trimeric IgA formation in HIGA mice.

Amino Acid Sequence↗
PubMed2004

[Diabetic nephropathy and plasminogen activator inhibitor 1 in urine samples].

Plasminogen activator inhibitor-1 (PAI-1) may contribute to renal fibrosis because of its involvement in matrix (ECM) accumulation through inhibition of plasmin-dependent ECM degradation. The aim of this study is to determine urinary PAI-1 concentrations and its intrarenal localization in patients with various renal diseases and to identify inducers for PAI-1 expression in human cultured proximal renal tubular cells (HRCs). Urinary PAI-1 concentrations were significantly higher in patients with overt diabetic nephropathy (DN, n=36) than in proliferative glomerulonephritis (PGN, n=8), nephrotic syndrome (NS, n=10) and healthy controls (n=12). Urinary PAI-1 concentrations (ng/gCr) were directly correlated with urinary N-acetyl glucosaminidase (NAG) levels (r=0.58, p<0.05). As for intrarenal localization of PAI-1 antigen, strong stainings for PAI-1 were observed in proximal tubular cells of renal biopsy samples from patients with DN, while no stainings for PAI-1 were found in renal tissues of PGN or NS. Immunoblot analysis revealed the presence of PAI-1 protein in whole cell lyzates from HRCs grown to semiconfluency. Exposure of growth-arrested HRCs with hypoxia (1% O2) or TNF-alpha (10 ng/ml) for 24 hours increased the secretion rate of PAI-1 protein by about 2.0-fold, while 24-hour treatment with high glucose (450 mg/dl) did not increase PAI-1 secretion at all, compared with that of the control cells under normal glucose (100 mg/dl) and normoxia (18% O2). These findings suggest that PAI-1 expression is upregulated especially in the proximal renal tubular cells of DN, which may be explained partially by hypoxia and inflammatory cytokines but not high glucose.

Diabetic Nephropathies↗
PubMed2003

Hepatic lipase mutation may reduce vascular disease prevalence in hemodialysis patients with high CETP levels.

BACKGROUND: Uremic dyslipidemia characterized by reduced high-density lipoprotein (HDL) cholesterol levels is one of the major contributors to the high incidence of cardiovascular disease in hemodialysis patients. Hepatic lipase (HL), together with cholesteryl ester transfer protein (CETP), may not only promote reverse cholesterol transport but also enhance production of small, dense, more atherogenic low-density lipoprotein (LDL). A common C-514T mutation of the promoter region of the HL gene reportedly increases HDL cholesterol levels. However, whether the HL mutation is antiatherogenic or proatherogenic has remained unknown in uremic patients and the general population. METHODS: We investigated the influence of the mutation and its interaction with CETP on HDL cholesterol levels and the apparent atherosclerotic complications in 183 hemodialysis patients aged over 30 years who had received no antilipemic drugs. RESULTS: In patients with CETP levels > or =2.2 microg/mL [high CETP (HCT) group, N = 97], subjects with the TT genotype had a significantly higher level of HDL cholesterol than those without TT genotype (56.8 +/- 15.9 mg/dL vs. 45.7 +/- 13.4 mg/dL, P < 0.001), but not in patients with CETP levels <2.2 microg/mL [low CETP (LCT) group]. Multiple linear regression analysis showed that the TT genotype was a major independent positive determinant for HDL cholesterol levels in the HCT not LCT group. Among the HCT group patients, subjects with the TT genotype (N = 25) had a tendency toward lower prevalence of vascular disease than those without TT genotype (N = 72) (4.0% vs. 22.2%, P < 0.07). In this subgroup, TT genotype had an independent odds ratio of 0.041 (95% CI 0.002 to 0.75, P < 0.05) after adjusting for other risk factors. CONCLUSION: The TT genotype of HL mutation may serve as a protective factor against vascular disease by increasing HDL cholesterol levels in hemodialysis patients with higher CETP levels.

Aged↗