[The clinical characteristics of neutrophil extracellular trap in patients with severe cerebral venous sinus thrombosis and its prognostic value in acute and subacute patients].

Objective: To explore the clinical characteristics of neutrophil extracellular trap (NET) in patients with severe cerebral venous sinus thrombosis (CVST) and to study their prognostic value in the acute and subacute phases. Methods: This study is a retrospective case series analysis. Clinical and pathological data of 52 patients with severe cerebral venous sinus thrombosis who underwent endovascular treatment in the Department of Neurosurgery, Tianjin Huanhu Hospital from June 2019 to June 2022 were retrospectively analyzed. There were 20 males and 32 females, with an age of (40.1±13.6) years(range:18 to 66 years). Forty-five healthy physical examinees were included in the control group. High-resolution MRI was used to stage the thrombus, with 11 cases in the acute group, 28 cases in the subacute group, and 13 cases in the chronic group. Thrombus specimens were obtained through endovascular treatment, and the fluorescence intensity of NET in peripheral blood at different time points was analyzed by immunofluorescence contrast,including the double-stranded DNA structure and adhesion protein components (citrolinated histone H3 (CitH3), myeloperoxidase-DNA complex(MPO-DNA), neutrophil elastase (NE)). The NET markers were determined by ELISA. Spearman rank correlation analysis was used to analyze the correlation between the NET markers in peripheral blood of patients with severe cerebral venous sinus thrombosis in the acute and subacute phases and the volume of venous sinus thrombus, the degree of venous sinus recanalization after treatment, and the discharge modified Rankin scale(mRS)score. The accuracy of NET markers in predicting the prognosis of patients with severe cerebral venous sinus thrombosis was analyzed by drawing receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Results: The results of immunofluorescence staining and ELISA showed that no NET structure was formed in the peripheral blood of the control group, while CitH3, MPO-DNA and NE levels in the peripheral blood of CVST patients were increased, among which the acute stage group was the highest, followed by the subacute group, and the chronic group was the lowest. Spearman correlation analysis showed that CitH3, MPO-DNA and NE levels in peripheral blood of patients in acute group and subacute group were positively correlated with thrombus volume and mRS score at discharge (P<0.05). The levels of CitH3 and MPO-DNA in peripheral blood of patients with complete venous sinus recanalization were lower than those of patients with partial venous sinus recanalization (P<0.01). ROC curve analysis results showed that MPO-DNA and NE had no predictive ability for the prognosis of CVST patients (P values were 0.614 and 0.324, respectively), and the AUC of CitH3 was 0.800 (95%CI: 0.638~0.962, P=0.032), the best cut-off value was 13.5 µg/L, the sensitivity was 100%, and the specificity was 58.8%. Conclusions: A large number of NET are formed in patients with severe cerebral venous sinus thrombosis in acute stage. Patients with severe cerebral venous sinus thrombosis in acute stage and subacute stage with high peripheral blood NET content has a low rate of complete sinus revascularization and poor neurological function recovery after treatment.

[Hepatitis B virus down-regulates the expression of inhibin and promotes the proliferation and survival of hepatocellular carcinoma cells].

Objective: To investigate the effect and role of the hepatitis B virus (HBV) on the expression of inhibin (PHB) in the proliferation and survival of hepatocellular carcinoma (HCC) cells. Methods: The expression of PHB in 13 pairs of HBV-infected livers, normal livers and HepG2.2.15 and HepG2 cells was detected by real-time fluorescent quantitative PCR and Western blot. Liver tissues were collected from seven patients with chronic hepatitis B before and after antiviral (tenofovir) treatment, and the expression of PHB was detected by RT-PCR and Western blot. HepG2.2.15 cells were transfected with Pcmv6-AC-GFP-PHB, and control vectors were collected. DNA content was analyzed by flow cytometry. The proliferation level of each cell group was detected using the EdU cell proliferation assay. HepG2.2.15 cells transfected with Pcmv6-AC-GFP-PHB and the control vector were cultured in serum-free medium for 6 days. Apoptosis was measured at the indicated time points using fluorescence-activated cell sorting (FACS)-based Annexin-V/PI double staining. Results: Compared with normal liver tissue, the expression of PHB in HBV-infected liver tissue was down-regulated (P < 0.01). Compared with HepG2 cells, the expression of PHB in HepG2.2.15 cells was significantly decreased (P < 0.01). The expression level of PHB in liver tissue after antiviral treatment (tenofovir) was significantly higher than that before treatment (P < 0.01). Compared with the control vector, the proliferation rate of HepG2.2.15 cells transfected with Pcmv6-AC-GFP-PHB was significantly lower than that of the control vector, and the apoptosis rate of HepG2.2.15 cells transfected with the Pcmv6-AC-GFP-PHB vector was significantly higher than the control vector (P < 0.01). Conclusion: HBV down-regulates the expression of inhibin to promote the proliferation and survival of hepatocellular carcinoma cells.

[Evaluation of papilledema and visual improvement in patients with idiopathic intracranial hypertension after venous sinus stenting].

Objective: To evaluate the improvement of papilledema and visual acuities in patients with idiopathic intracranial hypertension (IIH) after venous sinus stenting. Methods: The clinical data of 8 IIH patients who met the inclusion criteria underwent venous sinus stenting between January 2013 and December 2016 at Department of Neurosurgery, Tianjin Huanhu Hospital were analyzed retrospectively. There were 6 females and 3 males,aged (32.9±14.4)years (range:19 to 57 years).The thickness of the retinal nerve fiber layer (RNFL) was measured by optical coherence tomography. Fundus,visual acuity and visual field examination were performed before and after operation. If pressure gradient ≥10 mmHg(1 mmHg=0.133 kPa) across the venous stenosis was indicated by intraoperative pressure measurement,the patient would be treated with venous sinus stenting. Intracranial pressure was measured by lumbar puncture 3 to 7 days after operation. RNFL thickness and eye examination were detected 6 months after surgery. CT venogram was used to observe the sinus venous conditions. Paired t test was used to compare the data before and after surgery. Results: All the 8 patients underwent venous sinus stenting successfully. The mean pressure gradient across the venous stenosis was reduced from (24±9.2) mmHg to (2.6±2.0) mmHg (t=8.02,P<0.01). Intracranial pressure decreased from preoperative (41.4±12.7) cmH2O(1 cmH2O=0.098 kPa) to postoperative (12.9±3.3) cmH2O (t=7.08, P<0.01). The RNFL thickness decreased from (275.3±68.3)µm to (131.4±31.8)µm(t=5.80,P<0.05) 6 months after surgery and the baseline visual acuity was improved from(M(QR))0.24 (0.25) to 0.65 (0.23)(Z=-2.52,P<0.05).Papilledema was significantly improved in 6 patients,and no significant change in 2 patients. CT venogram indicated adjacent stent restenosis in 1 patient. Conclusion: Venous sinus stenting can effectively improve papilledema and visual acuity caused by IIH.

[Serum-and-glucocorticoid-inducible-kinase-2 is overexpressed and mediates glycogen synthase kinase-3ß/ ß-catenin signal transduction in hepatocellular carcinoma].

Objective: To investigate the differential expression of serum-and-glucocorticoid-inducible-kinase-2 (SGK2) in hepatocellular carcinoma (HCC) and normal liver tissues and the related mechanism mediating signal transduction of GSK-3 ß / ß catenin in HCC cells. Methods: Twenty pairs of matched HCC and normal tissues were collected and the situation of expression of SGK2 mRNA was detected by real-time fluorescence quantitative PCR. Western blot was used to detect the levels of SGK2 protein in human HCC cell lines (Huh-7, SMMC-7721) and normal human liver cell line (L02). SGK2 siRNA was used to transfect human HCC cell lines (SMMC-7721 and Huh-7), and then the protein expression levels of GSK-3 ß/ ß - catenin was successfully detected with the above-mentioned transfected cell line by western blot. Measurement data were expressed as mean ± standard deviation (x±s), and the Student t -test was used as the statistical method. Results: SGK2 mRNA expression was up-regulated in all 20 HCC samples than that of the expression of matched normal liver tissues. SGK2 protein levels were significantly higher in Huh-7 and SMMC-7721 than normal human liver cell lines (P < 0.01). The downregulation of SGK2 expression in human HCC cell lines (SMMC-7721 and Huh-7) had inhibited the expression of unphosphorylated GSK-3 ß. In addition, the downregulation of SGK2 expression in HCC cell lines had decreased the dephosphorylation of ß - catenin to prevent degradation of the ß - catenin proteasome. Conclusion: SGK2 is overexpressed in HCC and mediates GSK-3ß/ß- catenin signaling in HCC cells.

[Study of compound glutathione inosine injection effect on expression of regucalcin in liver tissue of rats with immune hepatic fibrosis].

Objective: To investigate the change in expression of anti-senescence marker protein calmodulin (RGN) in liver tissues of rats with immune hepatic fibrosis, and to observe the effect of compound glutathione inosine injection (CGII) on it. Methods: Rat liver fibrosis model was induced by intraperitoneal injection of porcine serum, and CGII intervention was administered at the appropriate time. Rat liver tissues were stained with HE and Masson. RGN and protein expression at mRNA in liver tissues was detected by fluorescence quantitative PCR and immunohistochemistry. One-way Anova was used for measurement data. LDS test was used for two-way comparison, and pathological semi-quantitative results were analyzed by rank-sum test. Results: The relative expression of RGN mRNA and protein in liver tissue of fibrotic rats was 82.23 ± 15.21 and 12.52 ± 3.23, respectively, which were significantly lower than that of normal rats 176.39 ± 11.35 and 59.23 ± 9.13 (P < 0.01). The degree of liver fibrosis in fibrotic rats after CGII intervention was significantly lower than fibrotic rats. The relative expression of RGN mRNA and protein in the intervention group was 168.78 ± 21.31 and 46.42 ± 4.71, respectively, which were significantly higher than fibrosis and spontaneous recovery group. The difference was statistically significant (P < 0.01). The relative expression of RGN mRNA and protein in the spontaneous recovery group was 86.23 ± 17.16 and 14.34 ± 5.16, which was higher than model group. The difference was not statistically significant (P > 0.05). Conclusion: The expression of RGN in liver tissue of rats with hepatic fibrosis induced by porcine serum is decreased, while the expression of RGN increases with the decrease of fibrosis after CGII intervention, suggesting that the protein may play an important role in the development of liver fibrosis.

[Study on the effect and mechanism of hepatitis B virus X protein transactivates gene 4 in HepG2 cell apoptosis].

Objective: To investigate the effect and mechanism of XTP4 gene in apoptotic hepatoblastoma HepG2 cell line. Methods: HepG2 cells were transiently transfected with small interfering RNA of XTP4 genes, plasmid pcDNA3.1/myc-His(-) A-XTP4, and hepatitis B virus X protein transactivated x gene 4 (HBX protein trans-activate gene4, XTP4) and their respective negative controls. After 48h, the overexpression and interference expression condition of XTP4 in HepG2 cells were detected by Western blot. HepG2 cells apoptosis was detected by flow cytometry. The expression levels of apoptosis-related proteins P53, Bcl-2, Bax and Caspase-3 in HepG2 cells were detected by Western blot, and Bcl-2/Bax ratio was calculated. The chemiluminescence assay was used to detect activity of caspase-3 in HepG2 cells. The measured data were presented as (x ± s), and independent sample t-test was used for comparison between the two groups. Results: HepG2 cells had successfully achieved the overexpression and interference expression of XTP4 protein. Compared with the control group, the overexpression of XTP4 in HepG2 cells had significantly decreased the number of apoptotic cells (P < 0.05), and increased Bcl-2/Bax (P < 0.05) ratio, but decreased the expression of P53 protein (P < 0.05). The protein expression of Caspase-3 and activity of caspase-3 was decreased (P < 0.05). However, interference with XTP4 expression in HepG2 cells had significantly increased the number of apoptotic cells (P < 0.05) and decreased Bcl-2/Bax (P < 0.05) ratio, but increased the expression of P53 protein (P < 0.05). The protein expression of Caspase-3 and activity of caspase-3 was increased (P<0.05). Conclusion: In HepG2 apoptosis XTP4 has inhibitory effect, and its effect on inhibiting HepG2 apoptosis may be achieved by regulating the Bcl-2/Bax ratio, and the P53 protein may be involved.

Antifungal activity of the bioactive substance from Bacillus atrophaeus strain HAB-5 and its toxicity assessment on Danio rerio.

The prevalence of pathogen inhibitors bacteria has motivate the study for antimicrobial compounds. Bioactive fungicide have always received considerable attention. A bacterial isolated strain HAB-5 showed antifungal activity against plant fungi. Based on morphological, physiological, biochemical and 16SrDNA sequence analysis, the strain was identified to be a Bacillus atrophaeus. This strain possessed a broad spectrum antifungal activity against various plant pathogenic fungi. Extraction of antifungal substance was performed and the crude extract had potent antifungal ability and showed great potential for swelling and inhibiting spore germination. This antifungal displayed heat stability and active in a wide pH range 5.0-10.0. Moreover no reduction was found in its activity after enzyme treatment. The toxicity test was evaluated in Danio rerio. The acute toxicity test indicated that the 24, 48, 72, 96h LC50 values of UMTLS to the zebrafish were 14.4, 13.8, 13.4, and 12.9%, respectively. Based on the results obtained in this study, antifungal substance was not toxic to zebra. Analyses of disease suppression showed that HAB-5 was effective to reduce the incidence of anthracnose symptoms on mango fruits, also prevent disease infection and protect tobacco seedling from Phytophtora nicotianae. The bioactive substance from Bacillus atrophaeus HAB-5 could be a candidate in the generation of new antifungal agents in crop.

Prognostic factors for treatment success in patients with multidrug-resistant tuberculosis in China.

OBJECTIVE: To examine the clinical outcomes and associated prognostic factors among patients with multidrug-resistant tuberculosis (MDR-TB) in China. METHODS: This retrospective study involved 243 patients with MDR-TB. All patients received standard regimens containing para-amino salicylic acid (PAS) and/or cycloserine (CS). The demographic, social and clinical characteristics of patients were recorded and the patients were followed up for 24 months. RESULTS: Treatment success was closely associated with young age, non-farming occupations, shorter history or smoking, normal urine results, initial MDR-TB treatment regimen, increased haemoglobin, direct bilirubin, uric acid and thyroid stimulating hormone (TSH) levels, and lower white blood cell, neutrophil and blood platelet counts (all P < 0.05). On multivariable analysis, increased haemoglobin (hazard ratio [HR] 1.019, 95%CI 1.007-1.032, P = 0.002) and TSH levels (HR 1.002, 95%CI 1.006-1.039, P = 0.008), normal urine results (HR 1.541, 95%CI 1.008-2.358, P = 0.046) and initial MDR-TB treatment regimen (HR 2.238, 95%CI 1.090-4.597, P = 0.028) were prognostic factors for treatment success in MDR-TB. CONCLUSIONS: Higher haemoglobin and TSH levels, normal urine results and initial MDR-TB treatment regimen might predict successful treatment of MDR-TB.

Effect of PM2.5 mediated oxidative stress on the innate immune cellular response of Der p1 treated human bronchial epithelial cells.

OBJECTIVE: To investigate the effect of stimulation of Human Bronchial Epithelial Cells (HBEC) by Der p1 and PM2.5 on the expression of innate immune cell factors to find new therapeutic targets for treatment of bronchial asthma. MATERIALS AND METHODS: The Der p1 antigen exposure model in the HEBC line, 16HBE-14o, was established in vitro. PM2.5 at a concentration of 50 µM/cm2, was added to these cells for 0.5 h, 1 h, 2 h and 3 h. Cells were treated with the following reagents for the indicated times: 300 ng/mL Der p1 for 21 h, 50 µM/cm2 PM2.5 for 3 h, 10 mM Nac for 3 h and PM2.5 contamination for 3 h. The experiment was divided into five groups: control (group A), Der p1 exposure group (group B), PM2.5 treated group (group C), PM2.5+Der p1 exposure group (group D), Nac+PM2.5+Der p1 exposure group (group E). ELISA method was adopted to test the expression levels of malondialdehyde, IL-25, IL-33 and thymic stromal lymphopoietin (TSLP), and Real-time RT-PCT was used to measure IL-25, IL-33 and TSLP mRNA. RESULTS: The protein and mRNA levels of malondialdehyde, IL-25, IL-33 and TSLP in group D were significantly higher than those in the other groups, while the protein and mRNA levels of malondialdehyde, IL-25, IL-33 and TSLP in group E were significantly lower than those in group D (p<0.05). CONCLUSIONS: PM2.5 can enhance the Der p1 antigen-induced HBEC innate immune response through the expression of IL-25, IL-33 and TSLP, which may exacerbate the occurrence rate of bronchial asthma.

Immunohistochemical evaluation of epidermal proliferation, differentiation and melanocytic density in symmetrical acrokeratoderma.

BACKGROUND: Symmetrical acrokeratoderma (SAK) is characterized by brown to black hyperkeratotic patches on acral regions. Although epidermal hyperkeratosis and acanthosis are consistent pathological changes, the nature of epidermal hyperplasia is unknown. AIM: To evaluate epidermal proliferation and differentiation and melanocytic density in skin lesions of SAK. METHODS: Expression of keratin 10 (K10), K14, K16, involucrin, filaggrin, Ki-67, and Melan-A was detected by immunohistochemistry in eight patients with SAK, seven patients with ichthyosis vulgaris (IV) and six healthy controls (HCs). RESULTS: Expression of K14, K16, involucrin and filaggrin was upregulated in patients with SAK compared with patients with IV and the HCs (P < 0.01-0.05), but K10 expression was similar for the three groups (P > 0.05). Numbers of Ki-67+ and Melan-A+ cells were higher in patients with SAK than in patients with IV and the HCs (P < 0.05). CONCLUSIONS: These results demonstrate that excessive keratinocyte proliferation and abnormal differentiation contribute to epidermal hyperplasia, while melanocytic proliferation is responsible for the pigmented lesions in SAK.

Neuroprotective effects of ginkgetin against neuroinjury in Parkinson's disease model induced by MPTP via chelating iron.

Disruption of neuronal iron homeostasis and oxidative stress are closely related to the pathogenesis of Parkinson's disease (PD). Ginkgetin, a natural biflavonoid isolated from leaves of Ginkgo biloba L, has many known effects, including anti-inflammatory, anti-influenza virus, and anti-fungal activities, but its underlying mechanism of the neuroprotective effects in PD remains unclear. The present study utilized PD models induced by 1-methyl-4-phenylpyridinium (MPP(+)) and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to explore the neuroprotective ability of ginkgetin in vivo and in vitro. Our results showed that ginkgetin could provide significant protection from MPP(+)-induced cell damage in vitro by decreasing the levels of intracellular reactive oxygen species and maintaining mitochondrial membrane potential. Meanwhile, ginkgetin dramatically inhibited cell apoptosis induced by MPP+ through the caspase-3 and Bcl2/Bax pathway. Moreover, ginkgetin significantly improved sensorimotor coordination in a mouse PD model induced by MPTP by dramatically inhibiting the decrease of tyrosine hydroxylase expression in the substantia nigra and superoxide dismutase activity in the striatum. Interestingly, ginkgetin could strongly chelate ferrous ion and thereby inhibit the increase of the intracellular labile iron pool through downregulating L-ferritin and upregulating transferrin receptor 1. These results indicate that the neuroprotective mechanism of ginkgetin against neurological injury induced by MPTP occurs via regulating iron homeostasis. Therefore, ginkgetin may provide neuroprotective therapy for PD and iron metabolism disorder related diseases.

The TNFAIP3 polymorphism rs610604 both associates with the risk of psoriasis vulgaris and affects the clinical severity.

BACKGROUND: Genome-wide association studies in white and Chinese Han populations have found that the single-nucleotide polymorphism (SNP) rs610604, at the tumour necrosis factor (TNF)-α-induced protein 3 (TNFAIP3) locus, is associated with psoriasis, and is also associated with response to TNF blockade in psoriasis. AIM: To examine whether this SNP is also associated with the clinical traits of psoriasis vulgaris (PV). METHODS: A hospital-based case-control study was performed, which involved 647 subjects [351 patients with PV and 296 healthy controls (HC)]. The rs610604 variants were typed using a SNaPshot assay. RESULTS: Both the G allele and the dominant model genotype (GG + GT) of rs610604 were associated with risk of PV (OR = 1.53; P = 0.01 and OR = 1.68, P < 0.01, respectively). In genotype-phenotype analysis, both the G allele and the GG + GT genotype were also associated with the clinical severity of PV. Severe cases [Psoriasis Area and Severity Index (PASI) > 6] had a higher frequency of the G allele and the GG + GT genotype compared with mild cases (PASI ≤ 6) (OR = 2.03, P = 0.001 and OR = 2.46, P < 0.001, respectively). In addition, rs610604 was significantly associated with almost all of the phenotypes in subphenotype-control analyses. CONCLUSIONS: SNP rs610604 in the TNFAIP3 locus is associated with the clinical severity of PV in a Chinese Han population.

Clinicopathological features and expression of four keratins (K10, K14, K17 and K19) in six cases of eruptive vellus hair cysts.

Six cases of eruptive vellus hair cysts (EVHC) were evaluated for histopathology and the immunohistochemical profile of Ki-67 and four keratins (K10, K14, K17 and K19). The pathological hallmark of EVHC was the existence of vellus hair shafts within the cystic cavity, but atypical pathological changes included two or three cysts and a foreign-body granuloma in three cases. Our results demonstrate that atypical pathological changes are not uncommon in EVHC, and indicate that based on keratin expression, it is likely that EVHC is derived from the infrainfundibulum and sebaceous duct.

A novel insertion mutation in the ADAR1 gene of a Chinese family with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant pigmentary genodermatosis, characterized by a mixture of hyperpigmented and hypopigmented macules that are mainly present on the dorsal portions of the extremities. The DSH locus was mapped to chromosome 1q11-q12 and, subsequently, pathogenic mutations in the double-stranded RNA-specific adenosine deaminase (ADAR1) gene were identified. We performed a mutational analysis of the ADAR1 gene in a Chinese family that included three individuals affected with typical DSH phenotypes. Mutations within the entire coding region and the exon-intron boundaries of ADAR1 were detected and confirmed by polymerase chain reaction and direct sequencing, respectively. An insertion mutation within exon 12, c.3035_3036insC (p.P1012fsX1017), was identified in all family members affected by DSH, but not in the healthy members or 100 unrelated controls. This finding improves our understanding of the role of ADAR1 in DSH.

Cutaneous phaeohyphomycosis caused by Exophiala spinifera in a patient with systemic lupus erythematosus.

Exophiala spinifera can induce both phaeohyphomycosis and chromomycosis. To date there have been 18 human infections caused by E. spinifera in the English literature. A case of E. spinifera-induced phaeohyphomycosis in a patient with systemic lupus erythematosus (SLE) is described. Direct microscopic examination of the pus showed branched, septate and chained hyphae and spores. A dark green velvety colony grew on Sabouraud dextrose agar. Slide culture showed branched, septate hyphae and spine-like annellated conidiophores. Histopathological biopsy revealed yellowish brown hyphae and spores. The isolate was identified as E. spinifera by DNA sequence analysis. The strain was unable to liquefy gelatin, grew at 25°C to 39°C, and was sensitive to itraconazole, amphotericin B, and terbinafine. To our knowledge, this is the first case of cutaneous phaeohyphomycosis caused by E. spinifera in SLE patients.

Hepatic lipase promoter C-480T polymorphism is associated with serum lipids levels, but not subclinical atherosclerosis: the Cardiovascular Risk in Young Finns Study.

The common C-480T polymorphism (rs1800588) of the hepatic lipase gene (LIPC) has been associated with high-density lipoprotein (HDL) cholesterol, atherosclerosis, and coronary artery disease. In this study, we examined whether the polymorphism is associated with serum lipid and lipoprotein concentrations, as well as with subclinical atherosclerosis in Young Finns. The participants comprised 2041 men and women (aged 24-39 years) enrolled in the Cardiovascular Risk in Young Finns Study with complete data concerning the rs1800588 polymorphism and serum lipids concentration. All participants underwent an ultrasound examination for brachial artery flow-mediated vasodilatation (FMD) and carotid artery intima-media thickness (IMT) measurement. The marker of arterial elasticity, carotid artery compliance (CAC), was also calculated by means of ultrasound and concomitant brachial blood pressure measurements. In all subjects, serum total cholesterol (p < 0.001), HDL cholesterol (p = 0.006), apolipoprotein AI (apoAI, p < 0.001), and triglyceride (p = 0.009) concentrations increased according to rs1800588 genotype in the order CC, CT, and TT. The same order applied only to apoAI after adjustment for age, body mass index, systolic and diastolic blood pressure, smoking, alcohol consumption, physical activity, diabetes, hypertension, contraceptive hormone use in women, and concentrations of glucose, insulin and C-reactive protein in men and women separately (p = 0.007 and p = 0.003, respectively). The polymorphism was also associated with HDL cholesterol, total cholesterol, and triglyceride levels in women (adjusted p = 0.004, p = 0.007 and 0.02, respectively), but not in men (p was not significant for all). No significant association between the rs1800588 and brachial FMD, carotid IMT, or CAC was found among the entire study population or among women or men separately, with or without adjustment for the above-mentioned factors. The rs1800588 is associated with serum lipid and apolipoprotein concentrations, especially in women, but does not seem to be a determinant of brachial artery FMD, carotid IMT, or CAC in young healthy adults.

The hepatic lipase gene C-480T polymorphism in the development of early coronary atherosclerosis: the Helsinki Sudden Death Study.

BACKGROUND: The T allele of the hepatic lipase (HL) C-480T polymorphism was previously found to be associated with lower post-heparin plasma HL activity, atherosclerosis and risk of coronary artery disease. We studied the association of HL C-480T polymorphism with the extent of atherosclerosis at vessel-wall level in an autopsy series of middle-aged men. MATERIALS AND METHODS: An autopsy cohort of 700 Caucasian Finnish men aged 33-70 years (mean 53 years), which comprised two autopsy series, collected 10 years apart during 1981-82 and 1991-92, were analysed. Areas of coronary wall covered with fatty streaks and fibrotic and complicated lesions were measured using computer-assisted planimetry and related to HL C-480T genotypes (CC, CT, and TT). RESULTS: There was a significant age-by-genotype interaction on the mean percentage area of fatty streaks (P = 0.01). The HL C-480T polymorphism was a significant explanatory factor for fatty streak area in men under 53 years of age with or without age, body mass index, hypertension, diabetes, smoking, alcohol consumption, apolipoprotein E genotype, and series number as covariates. Men carrying the TT genotype had two times larger areas of fatty streaks compared to the CC carriers (8.8% vs. 4.3%, P = 0.009). However, this association disappeared in men over 53 years. The areas of more advanced atherosclerotic lesions did not vary significantly among the genotype groups. CONCLUSIONS: Our results suggest that the HL C-480T polymorphism affects the formation of early coronary atherosclerotic lesions in men in their early middle age.