Biomedical subjects

L Zhang

Publications and source records attributed to L Zhang.

At least 199 records · Page 11Linked to original sources

PubMed2003

Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR.

Interferon stimulates the expression of a number of genes encoding enzymes with antiviral activities, including myxovirus resistance-1 (MxA), 2-5-oligoadenylate synthetase 1 (OAS-1) and double-stranded RNA-dependent protein kinase (PKR). We examined whether polymorphisms in these genes influenced the outcome of hepatitis C virus (HCV) infection. We observed a lower frequency of the GG genotype at position -88 in the MxA gene promoter in self-limiting HCV infection (OR=0.56; 95% CI: 0.35-0.8; P=0.010) and in nonresponders to therapy (OR=0.49; 95% CI: 0.25-0.95; P=0.020). This genotype predominantly influenced the outcome of treatment in patients with viral genotype 1 (OR=0.22 95% CI: 0.07-0.67; P=0.002). A polymorphism in the 3'-untranslated region of the OAS-1 gene was associated with outcome of infection (GG genotype less frequent in self-limiting infection: OR=0.43; 95% CI: 0.21-0.86; P=0.010). A polymorphism at position -168 in the promoter region of the PKR gene was associated with self-limiting infection (CT genotype: OR=2.75; 95% CI: 1.45-5.24; P=0.002). Further associations were found with a CGG trinucleotide repeat in the 5'UTR region of the PKR gene. Polymorphisms in the interferon-induced genes, MxA, OAS-1 and PKR appear thus associated with HCV outcome.

2',5'-Oligoadenylate Synthetase↗

PubMed2003

Targeted regulation of imprinted genes by synthetic zinc-finger transcription factors.

Epigenetic control of transcription is essential for mammalian development and its deregulation causes human disease. For example, loss of proper imprinting control at the IGF2-H19 domain is a hallmark of cancer and Beckwith-Wiedemann syndrome, with no targeted therapeutic approaches available. To address this deficiency, we engineered zinc-finger transcription proteins (ZFPs) that specifically activate or repress the IGF2 and H19 genes in a domain-dependent manner. Importantly, we used these ZFPs successfully to reactivate the transcriptionally silent IGF2 and H19 alleles, thus overriding the natural mechanism of imprinting and validating an entirely novel avenue for 'transcription therapy' of human disease.

Beckwith-Wiedemann Syndrome↗

PubMed2003

Focused ultrasound (HIFU) induces localized enhancement of reporter gene expression in rabbit carotid artery.

The development of accurate, safe, and efficient gene delivery remains a major challenge towards the realization of gene therapeutic prevention and treatment of cardiovascular diseases. In this study, we investigated the ability of high-intensity focused ultrasound (HIFU), a form of mechanical wave transmission, to act as a noninvasive tool for the enhancement of in vivo gene transfer into rabbit carotid arteries. Segments of the common carotid arteries of New Zealand white rabbits were isolated and infused with plasmid DNA encoding the reporter beta-galactosidase either with or without the addition of ultrasound contrast agent consisting of small (approximately 2-5 microm) gas-filled human albumin microspheres to augment cavitation. Infused arteries were exposed to pulsed ultrasound for 1 min (frequency 0.85 MHz, burst length 50 ms, repetition frequency 1 Hz, duration 60 s, peak pressure amplitude of 15 MPa). At 6.3 MPa, HIFU enhanced gene expression eight-fold, and 17.5-fold in the presence of contrast. We found increasing amounts of beta-galactosidase expression in the carotid vessel with increasing pressure amplitude. This dose-response relation was present with and without contrast. Without contrast, no vessel damage was detected up to 15 MPa, while the addition of contrast induced side effects above a threshold of 6.3 MPa peak pressure. The entire procedure was feasible and safe for the animals, and the results suggest that HIFU has the potential to assist in the noninvasive spatial regulation of gene transfer into the vascular system.

Animals↗

PubMed2003

Arsenic trioxide-induced mitotic arrest and apoptosis in acute promyelocytic leukemia cells.

Arsenic trioxide (As(2)O(3)), an effective drug for the treatment of acute promyelocytic leukemia (APL), can induce apoptosis and partial differentiation in APL cells in vitro and in vivo. However, As(2)O(3) also induces apoptosis in cancer cells other than APL with complex mechanisms, which seem to be cell type dependent. In this study, we report that APL cells (NB4 cell line) are arrested at early mitotic phase before the collapse of mitochondrial transmembrane potential (Deltavarphi(m)) and apoptosis after treatment with pharmacological concentrations (1.0-2.0 micro M) of As(2)O(3). We have also made the following new discoveries: (1) 0.5 micro M As(2)O(3) that fails to induce apoptosis has no effects on cell cycle distribution. (2) With inhibition of As(2)O(3)-induced Deltavarphi(m) collapse and apoptosis, dithiothreitol also effectively inhibits As(2)O(3)-induced mitotic arrest, suggesting that both As(2)O(3)-induced apoptosis and mitotic arrest involve proteins with thiol groups. (3) 1.5 mM caffeine that relieves cells from G(2)/M arrest also inhibits As(2)O(3)-induced Deltavarphi(m) collapse and apoptosis, (4) 1.0 micro M As(2)O(3) increases the expression of both cyclin B(1) and hCDC20 whereas it inhibits Tyr15 phosphorylation of p34(cdc2). In conclusion, our results strongly support that there is a tight link between As(2)O(3)-induced apoptosis and mitotic arrest, the latter being one of common mechanisms for As(2)O(3)-induced apoptosis in cancer cells.

Antineoplastic Agents↗

PubMed2003

Retrospective analysis of 1312 patients with haemophilia and related disorders in a single Chinese institute.

With 1.3 billion people, China has the largest population in the world, and therefore has the largest population of persons with haemophilia (PWH). As there is no national registry for haemophilia, it is difficult to ascertain how many PWH have actually been diagnosed. Between January 1983 and June 2002, 1312 patients with coagulation disorders were referred to our hospital, and 1190 patients were evaluable. Among them, 1069 (89.8%) patients had haemophilia, 68 had vWD, 20 had factor XI deficiency, 10 had acquired factor VIII inhibitor and 23 had other coagulation disorders. Of the 1069 PWH, 14.7% were unclassified, 38.4% severe, 35.7% moderate and 11.1% mild. If the unclassified cases were excluded, 45.1% were severe, 41.9% moderate and 13.0% mild. Twenty-nine of the 68 vWD patients had vWF:Ag <5%, and subcategorized as type 3 vWD. Because vWF multimer analysis was not performed in our centre, the remaining vWD patients were not subdivided.

Adolescent↗

PubMed2003

Changes in the distribution pattern of gelatin-binding protein of 28 kDa (adiponectin) in myocardial remodelling after ischaemic injury.

AIMS: Gelatin-binding protein of 28 kDa (GBP28) is a collagen-like plasma protein having a binding capacity with collagens. We investigated GBP28 role on myocardial remodelling as well as the diagnostic significance of GBP28 immunostaining in myocardial infarction. METHODS AND RESULTS: Myocardial tissues obtained from 47 autopsied hearts with infarction were immunostained with antibodies against GBP28, fibronectin, type III and IV collagens, and prolyl 4-hydroxylase. GBP28 was distributed in interstitium of infarcted lesions at an early stage. GBP28 was linearly found both along the border with vital myocardium and at the periphery of surviving cardiomyocyte around the lesion at granulative stage. However, it was not observed in the scar. GBP28 distribution patterns were similar to those of fibronectin in infarcted lesions and those of type IV collagen at the periphery of cardiomyocyte. Type III collagen was not recognized in the early-stage lesion but increased along with scar maturation. Prolyl 4-hydroxylase was found in surviving cardiomyocytes around the lesion during all stages and in interstitial cells appeared in granulation tissue. CONCLUSION: GBP28 plays a role as a scaffold of newly formed collagen in myocardial remodelling after ischaemic injury, and GBP28 immunostaining may assist in a diagnosis of healing stage.

Adiponectin↗

PubMed2003

Chemosensory proteins of Locusta migratoria.

Two different classes of chemosensory proteins (CSPs) in Locusta migratoria have been identified on the basis of the molecular cloning of a series of different cDNAs from the antennae of this insect. Several CSP isoforms have been purified and biochemically characterized from antennal and wing extracts, some of them corresponding to expression products predicted for the identified cDNAs. In wings, the nature of the main endogenous ligand binding to these proteins was determined as oleoamide by a gas chromatography-mass spectrometric approach. One of these isoforms has been expressed in a bacterial system with high yield and used in a fluorescent binding assay. Competitive binding experiments have indicated the presence of long-chain compounds among the best ligands.

Amino Acid Sequence↗

PubMed2003

Factors predictive of nephropathy in DCCT Type 1 diabetic patients with good or poor metabolic control.

AIMS: The study aim was to assess the time-related risk of developing diabetic nephropathy [albumin excretion rate (AER) > or =40 mg/24 h] from baseline covariates in Type 1 diabetic patients with either good or poor metabolic control (MC). METHODS: Based on material from the Diabetes Control and Complications Trial study (n=1441), patients were considered as under good or poor MC if their HbA1c mean level up to last visit fell in the lowest (< or =6.9%) or highest (>or =9.5%) quintile of the overall HbA1c distribution, respectively. Prevalence cases of nephropathy were excluded from the study. Survival analysis and Cox regression were applied to the data. RESULTS: Among patients with good MC (n=277), 15% had developed nephropathy at the end of the study. Conversely, among patients with poor MC (n=268), the proportion without the complication was 52%. When adjusting for MC, time to diabetic nephropathy was related to age (P<0.0001), AER (P<0.001), duration of diabetes (P<0.005), body mass index (BMI) (P<0.005), all at baseline, and to gender (P<0.01). Patients with upper normal range AER levels, longer duration of diabetes and lower BMI were at higher risk, regardless of MC. The adverse effect of younger age on diabetic nephropathy was more marked in good than in poor MC. Although women tended to develop the complication more often under good MC, they appeared to be better protected under poor MC. CONCLUSIONS: This study confirms occurrence of diabetic nephropathy under good MC and non-occurrence of the complication despite poor MC. It also demonstrates that some baseline covariates can affect, in a differential manner, time to diabetic nephropathy depending on MC.

Adolescent↗

PubMed2003

Endogenous plasmin converts Glu-plasminogen to Lys-plasminogen on the monocytoid cell surface.

Recently, we showed that localization of Glu-plasminogen on cell surfaces enhances its conversion to Lys-plasminogen by exogenous plasmin. This leads to stimulation of plasminogen activation because Lys-plasminogen is the preferred substrate on cell surfaces. Here, we show that Glu-plasminogen was converted to Lys-plasminogen on monocytoid cells in the absence of exogenous plasmin. Culture of cells under serum-free conditions did not affect this conversion, suggesting that the enzymatic activity was cell-derived. Therefore, we tested whether endogenous monocytoid plasminogen could provide a source of plasmin to convert cell-associated Glu-plasminogen to Lys-plasminogen because plasmin is the only enzyme known to effect this reaction. We used a recombinant human plasminogen mutant, [D(646)E]Pg, which can be cleaved by plasminogen activators, but cannot catalyze the generation of Lys-plasminogen. Upon incubation with either THP-1 or U937 monocytoid cells, 35 and 38%, respectively, of the cell-bound ligand was converted to Lys-[D(646)E]Pg. Trasylol, alpha2-antiplasmin, and an anticatalytic antiplasminogen monoclonal antibody decreased Lys-[D(646)E]Pg formation to < 5% on monocytoid cells, consistent with a plasmin-dependent mechanism. Plasminogen was detected in these cells by Northern blotting and RT-PCR. Our results suggest that plasmin converts cell-bound Glu-plasminogen to Lys-plasminogen and that this enzyme is produced by activation of monocytoid plasminogen by endogenous monocytoid plasminogen activators to enhance plasminogen activation on the monocytoid cell surface.

Cell Line↗

PubMed2003

Noninvasive analysis of conjunctival microcirculation during carotid artery surgery reveals microvascular evidence of collateral compensation and stenosis-dependent adaptation.

OBJECTIVE: Hemodynamically relevant internal carotid artery (ICA) stenosis is a major cause of ischemic stroke. Despite its long-term benefit, carotid endarterectomy may also be associated with severe neurologic deficits. Intraoperative and early recognition of ischemia in the region of the ICA may reduce this risk. To date, direct imaging and quantitative analysis of microvascular structures and function in the human ICA region have not been possible. We purposed to visualize and quantify ischemia/reperfusion-induced microcirculatory changes in the terminal vascular bed of the ICA in patients undergoing unilateral ICA endarterectomy. METHODS: Sequential analysis of the ipsilateral and contralateral conjunctival microcirculation was performed with orthogonal polarized spectral imaging in 33 patients undergoing unilateral ICA endarterectomy because of moderate or severe ICA stenosis (North American Symptomatic Carotid Endarterectomy Trial score, 75% +/- 13%), before clamping the ICA (baseline), during clamping of the external carotid artery and ICA, during reperfusion of the ICA (intraluminal shunt), during the second clamping of the ICA (shunt removal), after declamping (reperfusion) of the external carotid artery and ICA, and 15 to 20 minutes after the second ICA reperfusion. RESULTS: During ICA clamping for shunt placement, ipsilateral and contralateral conjunctival capillary perfusion was significantly decreased, but it was completely restored after reperfusion with carotid shunting. Reclamping of the ICA for shunt removal caused microvascular dysfunction, which was significantly less pronounced than that observed during the first clamping. The individual degree of ICA stenosis was inversely correlated with the ipsilateral and contralateral decrease in conjunctival functional capillary density during the first ICA clamping. CONCLUSIONS: These results suggest adaptive mechanisms of capillary perfusion with increasing stenosis and development of collateral compensatory circulation in the vascular region of the human ICA. Conjunctival orthogonal polarized spectral imaging during unilateral ICA reconstruction enables continuous noninvasive analysis of bilateral conjunctival microcirculation in the terminal region of the ICA and enables monitoring for efficient carotid shunt perfusion during and after endarterectomy.

Adaptation, Physiological↗

PubMed2003

Single- and repeated-dose pharmacokinetics of eplerenone, a selective aldosterone receptor blocker, in rats.

1. The pharmacokinetics of eplerenone (EP) were examined in rats following single or repeated dosing with (14)C-labelled or unlabelled EP to characterize absorption, metabolism and excretion. Rates of EP metabolism and cytochrome P450 activities were determined in vitro after repeated dose administration of EP. 2. Following a single i.v. dose (15 mg kg(-1)), the elimination half-life of EP was 0.80 and 1.14 h in male and female rats, respectively. Plasma clearances (CL) of EP were 1.62 and 1.20 l kg(-1) h(-1) in males and females, respectively. Following a single oral dose (15 mg kg(-1)), C(max) and T(max) of EP were 1.71 micro g ml(-1) and 0.5 h in male rats. The corresponding values in female rats were 3.54 micro g ml(-1) and 1.0 h. The systemic availability of EP was 25.6% in male rats and 66.4% in female rats, demonstrating sex differences in the pharmacokinetics of EP. 3. In the 8-day study, the AUC(0-24h)'s of total EP (closed lactone ring form plus open form) following 100 and 200 mg kg(-1) oral doses were approximately half those on day 1 in male rats. After repeated dosing for 13 weeks, the pharmacokinetics of total EP did not change with study duration at the 20 mg kg(-1) dose in both males and females. However, at the 100 mg kg(-1) dose, AUC(0-24h)'s were notably reduced on day 24 but progressively increased on subsequent days to approximate day 1 levels by day 86 in both sexes. At the 500 mg kg(-1) dose, the AUCs on day 86 remained lower than those on day 1. Reductions in AUCs on days 8 and 24 appeared to be the result of metabolism induction. 4. EP was extensively metabolized in male rats and most faecal and urinary radioactivity was in the form of metabolites. In female rats, the vast majority of urine and faecal radioactivity was associated with total EP. Thus, the sex difference in the pharmakokinetics of EP was due to more extensive metabolism in male rats. 5. The major metabolite in the rat was 6beta-OH EP. EP 6beta-hydroxylase activity was well correlated with testosterone 6beta-hydroxylase activity, indicating that EP metabolism to 6beta-OH EP was mediated primarily by CYP3A in the rat. 6. After repeated dose administration, EP increased 6beta-hydroxylase activities of testosterone and EP itself in a dose-dependent manner in both male and female rats, indicating that EP was a CYP3A inducer in the rat. There appeared to be no effects on activities of CYP1A1, 2B and 2E1.

Administration, Oral↗

PubMed2003

Severe acute respiratory syndrome: global initiatives for disease diagnosis.

We present a retrospective analysis of the available articles on severe acute respiratory syndrome (SARS) published since the outbreak of the disease. SARS is a new infectious disease caused by a novel coronavirus. Originating in Guangdong, Southern China, at the end of 2002, it has spread to regions all over the world, affecting more than 8000 people. With high morbidity and mortality, SARS is an important respiratory disease which may be encountered world-wide. The causative virus was identified by a WHO-led network of laboratories, which identified the genome sequence and developed the first molecular assays for diagnosis. For the respiratory physician, detecting SARS in its earliest stages, identifying pathways of transmission, and implementing preventive and therapeutic strategies are all important. The WHO and the CDC have published helpful definitions of 'suspected' and 'probable' cases. However, the symptoms of the disease may change, and laboratory tests and definitions are still limited. Even in a situation of no new cases of infection, SARS remains a major respiratory health hazard. As with influenza virus outbreaks, new epidemics may arise at the end of each year.

Antibodies, Viral↗

PubMed2003

Evidence that nuclear factor-kappa B activation is critical in oxidant-induced disruption of the microtubule cytoskeleton and barrier integrity and that its inactivation is essential in epidermal growth factor-mediated protection of the monolayers of intestinal epithelia.

Using monolayers of intestinal (Caco-2) cells, we showed that oxidants disrupt the microtubule cytoskeleton and barrier integrity; epidermal growth factor (EGF) was protective via stabilization of the microtubules. Because proinflammatory conditions activate nuclear factor-kappaB (NF-kappaB), we hypothesized that oxidants disrupt barrier integrity through activation of NF-kappaB and that EGF protects by suppressing NF-kappaB. Parental cells were pretreated with EGF or NF-kappaB or inhibitory kappaBalpha (I-kappaBalpha) modulators. Other cells were stably transfected with varying levels of a dominant negative mutant for the NF-kappaB inhibitor I-kappaBalpha. Both types of cells were grown as monolayers and then exposed to oxidant (H2O2). We then monitored monolayer barrier integrity (permeability), stability of the microtubule cytoskeleton (confocal microscopy, immunoblotting), intracellular levels of the I-kappaBalpha (immunoblotting), translocation, and activity of NF-kappaB (immunoblotting, sensitive enzyme-linked immunosorbent assay). Monolayers were also fractionated and processed to assess alterations in 1) polymerized tubulin (S2; an index of cytoskeletal integrity) and 2) monomeric tubulin (S1; an index of disassembly) (polyacrylamide gel electrophoresis fractionation and immunoblotting). We found the following: 1) Oxidants caused I-kappaBalpha degradation, NF-kappaB translocation, NF-kappaB (p50 and p65 subunits) activation, tubulin disassembly ( upward arrow S1, downward arrow S2), microtubule architectural instability, and barrier disruption. I-kappaBalpha stabilizers and NF-kappaB inhibitors [e.g., carbobenzyloxy-leuleu-leucinol (MG-132), lactacystin] suppressed oxidants injurious effects. 2) EGF (10 ng/ml) stabilized I-kappaBalpha and prevented both NF-kappaB translocation and activation while protecting monolayers against oxidants. 3) In stably transfected cells, transfection-induced stabilization of I-kappaBalpha by itself led to EGF-like protective effects. In these mutant cells, protection was not potentiated by EGF (10 ng/ml). Conclusions are 1) oxidants induce disruption of the cytoskeleton and intestinal barrier integrity, in part, through I-kappaBalpha degradation and subsequent NF-kappaB activation, 2) I-kappaBalpha stabilization is by itself protective, mimicking EGF, and 3) EGF protects cell monolayers through I-kappaBalpha stabilization and NF-kappaB inactivation. To our knowledge, this is the first report that NF-kappaB can affect the dynamics of cytoskeletal assembly and intestinal barrier integrity.

Biological Transport↗

PubMed2003

Fulminant Crohn's colitis after allogeneic stem cell transplantation.

We report a case of fulminant Crohn's colitis that occurred following non-myeloablative allogeneic stem cell transplantation for Hodgkin's lymphoma. Adoptive transfer of inflammatory bowel disease by haematopoietic cells is recognised in several animal models of inflammatory bowel disease and remission of Crohn's disease has been reported in patients who have received a bone marrow transplant. However, adoptive transfer of Crohn's disease susceptibility leading to phenotypic manifestation of the disease after transplantation has not been previously reported. Having ruled out an infective cause of a colitis in this case, we speculated that adoptive transfer of Crohn's disease may have occurred and performed a genetic analysis of known susceptibility loci for significant donor-recipient mismatches. The donor and recipient had several haplotype mismatches in HLA class III genes at the IBD3 locus. In addition, the donor (but not the recipient) had a polymorphism of the 5' UTR of NOD2/CARD15 that may be associated with Crohn's disease. This case highlights the question of whether adoptive transfer of Crohn's disease can occur between allogeneic stem cell transplant donor and recipient, in a similar fashion to that reported for other autoimmune diseases. This report should also stimulate debate regarding the need for stem cell transplant donor screening for inflammatory bowel disease.

5' Untranslated Regions↗

PubMed2003

Cloning and characterization of a novel splicing variant of the ZADH1 gene.

We report here the cloning and characterization of a novel splicing variant of the human zinc binding alcohol dehydrogenase, domain containing 1 (ZADH1) gene. ZADH1 is localized on chromosome 14q24.2. The cDNA of this splicing variant is 1613 base pairs in length, and encodes a 351-amino acid protein with a putative molecular weight of 38.5 kDa. We named the novel splicing variant ZADH1b. By MTC- panel PCR analysis, it was found that ZADH1b was widely expressed in human tissues. Computer analysis revealed ZADH1 had a potential ADH_zinc_N domain and it had considerable homology with some dehydrogenases. It was speculated that ZADH1 may have definite metabolic roles in vivo as a dehydrogenase.

15-Oxoprostaglandin 13-Reductase↗

PubMed2003

Sonographic reproducibility of a novel approach in the assessment of centralised access in end-stage renal disease.

A reliable and accurate non-invasive test is needed to help determine grafts and/or fistulae in end-stage renal disease (ESRD) patients. Sonographic scanning to assess the state of the fistula and AV shunt seems underused. To find out what role B-mode and Doppler play in the assessment of fistula and shunt, we scanned nine patients with a fistula as central access and nine patients with a graft several times over a period of a month. Diameters were measured before and after the AV shunt and Doppler measurements were made pre, inter and post shunt. We established that B-mode measurements are reliable in predicting the future and integrity of both fistulae and grafts. Doppler measurements were less consistent and therefore less reliable. The average initial measurement showed a screen of 5.766 mm and a second measurement of 5.890 mm; The coefficient of variation (CV)/reproducibility was 1.58% for first measurement. The average first and second measurements post graft were 6.317 mm and 6.365 mm, respectively. The CV/reproducibility was 0.48%. First and second peak flow measurements averaged 149 m/s and 112 m/s, respectively, resulting in a CV of 14.0%. We conclude that morphological changes may be more reliable than Doppler values, indicating a potentially greater use for B-mode ultrasound in predicting an open shunt and/or fistula.

Adolescent↗

PubMed2003

[Prevention of lower limb necrosis and amputation by femoro-crural bypass: indications, techniques and results].

Limb threatening ischemia is a challenge for the vascular surgeon. Recent progress in revascularization procedures allow to minimize the primary amputation rate in the management of chronic critical limb ischemia. The authors discuss the prevalence and causes of chronic critical limb ischemia, with a special interest for diabetic arteriopathy. The technique of crural and pedal vessel revascularization is described, as well as the innovative tourniquet technique for distal bypass surgery. A review of published series of infrapopliteal bypass surgery is made. The experience of the authors during last decade with crural and pedal bypass surgery is analyzed.

Arteries↗

PubMed2002

Single-nucleotide polymorphisms in the lipoprotein lipase gene associated with coronary heart disease in Chinese.

Coronary heart disease is a complex disease reflecting the interaction of multiple genes with the environment (e.g. diet, life style). Lipoprotein lipase (LPL) plays an important role in lipid metabolism and the pathogenesis of coronary atherosclerosis. Recent associations between single-nucleotide polymorphisms in the LPL gene and heart disease have been reported, but little is known in Chinese. The LPL gene spans >26 kb, with an mRNA of 3549 bp. In the present study, we screened 5155 bp (565 bp of 5' flanking region, nine exons and donor- and acceptor-splice sites, and some intronic bases) in 160 Chinese patients with confirmed coronary heart disease and 150 age- and gender-matched controls. Thirteen of the sixteen single-nucleotide polymorphisms that we found have not been previously reported. In males, significant (P<0.05) differences between the coronary heart disease patients and controls were found for five single-nucleotide polymorphisms: -421G>A (5' flanking region); +13,577C>A (intron 2); +16,052G>A, R192Q (exon 5); +16,173C>G and +16,177T>C (intron 5). In females, significant differences between the patients with coronary heart disease and controls were found for only the -421G>A and +16,052G>A (R192Q) mutations. Among the coronary heart disease males, significant (P<0.05) associations were found between the low-HDL high-triglyceride (LHDL/HTG) phenotype and the non-LHDL/HTG trait for the 5' flanking-421G, the intron 2+13,577C, and the exon 5+16,052G mutations, with odds-ratios (ORs)[confidence intervals] of 3.90[1.12-13.66], 3.38[1.22-9.40], and 3.22[1.04-10.01], respectively; no corresponding associations were found in females. There were 69, 51, 57 and 41 unphased haplotype patterns in male coronary heart disease, male control, female coronary heart disease and female control groups, respectively; the computer program PM-Plus found the heterogeneity model by far the best fit (P<0.0001 in males, >0.01 in females). These data show that some single-nucleotide polymorphisms in the LPL gene among Chinese are associated with abnormal lipid and lipoprotein profiles and predisposition to coronary heart disease, a genetically heterogeneous complex disease, and that they are gender-specific.

Adult↗