ABSTRACT
BACKGROUND: We investigated the relationships between the ALOX5AP gene rs10507391 and rs4769874 polymorphisms, serum levels of leukotriene (LT) B4, and risk of acute coronary syndrome (ACS). METHODS: A total of 709 participants, comprising 508 ACS patients (ACS group) and 201 noncoronary artery disease patients with chest pain (control group) were recruited from the Han population of the Changwu region in China. Two polymorphic loci were genotyped using polymerase chain reaction and restriction fragment length polymorphism analysis. Serum LTB4 level was determined by enzyme-linked immunosorbent assay. RESULTS: Serum LTB4 levels were significantly higher (P<0.001) in the ACS group (median/interquartile range, 470.27/316.32 pg/ml) than in the control group (233.05/226.82 pg/ml). No statistical differences were observed between genotype, allele and haplotype frequencies for the tested loci in either the ACS group or the control group, even after adjustments were made for conventional risk factors by multivariate logistic regression. This suggests there is no association between the ALOX5AP rs10507391 and rs4769874 polymorphisms and ACS risk. Elevated serum LTB4 level was closely linked to ACS risk, and may be independent of traditional risk factors as a risk factor for ACS (P<0.001). There was no significant association between serum LTB4 levels and the two variants in either the ACS group or the control group. CONCLUSIONS: Rs10507391, rs4769874 and its haplotypes in ALOX5AP are unrelated to ACS risk in the Chinese Han population of Changwu, but elevated serum LTB4 level is strongly associated with ACS risk. Serum LTB4 level is not subject to the influence of either the rs10507391, rs4769874 or the haplotype.
Subject(s)
5-Lipoxygenase-Activating Proteins/genetics , Acute Coronary Syndrome/genetics , Genetic Predisposition to Disease , Leukotriene B4/genetics , Acute Coronary Syndrome/pathology , Aged , Alleles , Asian People , China , Female , Genetic Association Studies , Haplotypes , Humans , Male , Middle Aged , Polymorphism, Single NucleotideABSTRACT
AIM: To investigate the distribution of killer cell immunoglobulin-like receptor (KIR) and its specific ligand human leukocyte antigen (HLA) in Jiangsu Han population. METHODS: 173 samples from unrelated healthy individuals of Jiangsu Han population were genotyped and observed for KIR, HLA-Cw and HLA-Bw4 using a SYBR Green I real-time PCR and PCR-SSP method, respectively. The number and type of KIR/HLA pairs inherited in each individual were analyzed. RESULTS: In Jiangsu Han population, all four inhibitory KIR (2DL1, 2DL2/3, 3DL1 and 3DL2) that recognize the classical HLA class I molecules HLA-A, -B and -C were present in >92% of the study group. Frequencies of 2DL2/HLA-C1, 2DL3/HLA-C1, 2DL1/HLA-C2 and 3DL1/Bw4 were 0.243, 0.971, 0.457 and 0.590, respectively; frequencies of 2DS1/HLA-C2 and 2DS2/HLA-C1 were 0.162 and 0.231, respectively. 54.3% of the cases expressed KIR2DL1 without HLA-C1, 32.9% inherited 3DL1 without HLA-Bw4 and 5.8% expressed HLA-Bw4 without 3DL1. 27.7% of the individuals had three iKIR/HLA pairs, 26% carried two iKIR/HLA pairs, and 25.4% inherited a single iKIR/HLA pair and no one was deficient in all three iKIR/HLA pairs. CONCLUSION: There was disparity between KIR receptor and HLA ligand in Jiangsu Han population. Inhibitory KIR/HLA pair frequency was higher than stimulatory one. About 1/4 of the study group expressed a single iKIR/HLA pair alone.
Subject(s)
Receptors, KIR/genetics , China/ethnology , Gene Frequency , Genotyping Techniques , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/immunology , Histocompatibility Testing , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Ligands , Receptors, KIR/immunologyABSTRACT
Endothelial lipase (EL) is a novel member of the triglyceride (TG) lipase family. A growing body of evidence has indicated that EL gene polymorphism might contribute to the process of cardiovascular diseases. This study was aimed to reveal the potential relationship between EL -384A/C gene polymorphism and acute coronary syndrome (ACS) in a Chinese Han population. The subjects were composed of 320 ACS patients and 315 age- and gender- matched controls. We detected the EL -384A/C genotypes and allele frequencies by using polymerase chain reaction-restriction fragment length polymorphism analysis. There was significant difference in AA genotype and AC+CC genotype between ACS and control groups (P = 0.014). The A allele frequency was significantly higher in ACS group than in control group (87.8 vs 83.8 %, P = 0.041). The relationship between the variant and ACS remained significant after adjusting for current smoker, hypertension, diabetes mellitus, total cholesterol and TG (OR = 0.682, 95 % CI = 0.472-0.986). The levels of HDL and ApoA-I were significantly higher in AC+CC genotype than in AA genotype (HDL: 1.20 ± 0.35 vs 1.11 ± 0.29 mmol/L, P = 0.001; ApoA-I: 1.14 ± 0.25 vs 1.08 ± 0.21 g/L, P = 0.009). We found that the EL -384A/C gene polymorphism might be associated with ACS in Chinese Han population, suggesting that the variant might be involved in the pathogenesis of ACS.
Subject(s)
Acute Coronary Syndrome/genetics , Lipase/genetics , Polymorphism, Single Nucleotide , Acute Coronary Syndrome/ethnology , Aged , Asian People , Case-Control Studies , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Polymorphism, Restriction Fragment LengthABSTRACT
AIM: To develope a novel real-time PCR method for KIR genotyping. METHODS: KIR genotyping is performed using 16 real-time PCR reactions, each containing two-three KIR-specific primers, a pair of internal positive control primers and a fluorescence dye, SYBR Green I. By the analysis of the Tm and the characteristic of the melting curve of the amplified products, we identified the presence or absence of 16 KIR genes. A variety of dilution folds were made to detect the sensitivity of this method. RESULTS: KIR genes were effectively genotyped by the analysis of the melting curve. This method can be used to detect KIR genes even from 0.1 ng of DNA. The feasibility of this method was tested by genotyping 10 DNA samples from Peripheral blood and 10 DNA samples from cervical cell. CONCLUSION: We developed a novel real-time PCR assay with SYBR Green I, which is a simple, rapid, sensitive, real-time and environmental method. It provides the possibility of the automated KIR genotyping.
Subject(s)
Organic Chemicals , Real-Time Polymerase Chain Reaction/methods , Receptors, KIR/genetics , Benzothiazoles , Diamines , Genotyping Techniques , Humans , QuinolinesABSTRACT
Erythropoietin (EPO) has a neuroprotective effect in the animal model of ischemia/hypoxia, but the mechanisms underlying the EPO effect in traumatic brain injury (TBI) are not well understood. This study examined the potential neuroprotective mechanisms of recombinant human EPO (rhEPO) in rats after TBI. Sixty healthy adult male Sprague-Dawley rats were randomly divided into 5 groups: 1000 U/kg rhEPO-treated, 3000 U/kg rhEPO-treated, 5000 U/kg rhEPO-treated, citicoline, and normal saline (control) groups. The TBI model was based on the modified Feeney's free falling model. Serum samples were collected at 6 hours, 24 hours, 3 days, 5 days, and 7 days after trauma. The serum S100B protein and interleukin-6 (IL-6) levels were measured after treatment in each group with double antibody sandwich enzyme-linked immunosorbent assay. Both serum S100B protein and IL-6 levels were significantly lower in 3000 U/kg rhEPO-treated and 5000 U/kg rhEPO-treated groups (p < 0.001). The decrease in serum S100B protein level was correlated with the dosage of rhEPO. Medium doses of rhEPO achieved the optimum decreases in the serum IL-6 level. Therefore, inhibition of the composition and secretion of S100B protein and IL-6 levels by EPO might be one of the mechanisms involved in decreasing inflammatory reaction in the brain, and may be responsible for the neuroprotective effect after TBI.
