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Effect of Variation in CHI3L1 on Plasma YKL-40 Level, Risk of Asthma, and Lung Function

Author: ShaoJinLian
Tutor: LuoYaLing
School: Southern Medical University,
Course: Respiratory System Diseases
Keywords: Asthma CHI3L1 Single nucleotide polymorphisms (SNPs) YKL-40 Lung function Eosinophils
CLC: R562.25
Type: Master's thesis
Year: 2011
Downloads: 29
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Abstract


Background Bronchial asthma is a variety of cells, inflammatory mediators and cytokines mediated by a complex immune mechanism airway chronic inflammatory diseases. The same time, is also a complex multi-gene diseases with genetic predisposition, was the familial aggregation of its occurrence, development interactions determined by the patient's genetic predisposition and environmental exposure. At home and abroad asthma has conducted a lot of research, a growing number of researchers dedicated to the genetic etiology of the disease, so far there are a large number of studies attempting to probe the crowd with asthma susceptibility gene, hope susceptible to asthma gene determination to help people better understand the pathophysiology of asthma, and also provide help to find an effective asthma treatment program. Chitin (Chitin) is a natural content of polysaccharides, is widely found in the cell walls of bacteria, fungi, crustaceans, arthropods and other lower organisms. Chitin can be some special enzymatic degradation, so these enzymes are known as crustaceans enzyme, which is highly conserved in evolution hydrolase family. Recent studies have found functional the crustaceans enzyme gene and some crustaceans enzyme similar genes, the latter genes encoding proteins with chitin binding but not catalytic chitin. Animal and human studies have shown that the the crustacean enzyme, and crustaceans enzyme similar proteins are natural immune response to the potential positive and negative regulatory factor. CHI3L1 gene is similar to a crustacean enzyme gene, located on chromosome 1q32.1, it encodes YKL-40 or human cartilage glycoprotein 39 (HCgp-39) is a 40-kD mammalian glycoproteins. YKL-40 lacks the characteristics of the enzyme, but it can be combined with the widely expressed crustaceans sugar, which participate in the inflammation and tissue remodeling. Expression of YKL-40 is associated with certain diseases, tissue inflammation and remodeling and cell growth abnormal pathological features, such as atherosclerosis, schizophrenia, liver fibrosis, and some cancers. Recent studies suggest that in asthmatic patients, serum YKL-40 levels are elevated, the level of YKL-40 in the cycle, with the severity of asthma, subepithelial basement membrane thickness and lung function related. The CHI3L1 gene comprises 10 exons in the the CHI3L1 gene promoter region, there-131C / G (rs4950928),-247C / T (rs10399805), and-329G / A (rs10399931) three single nucleotide polymorphisms with serum YKL-40. rs4950928G allele of the Chinese people is schizophrenia risk factors of the population of Europe, Europe and America, it is asthma, airway hyperresponsiveness and lung function to reduce the protection factor (does not affect the risk of allergies), Europeans, but also increase the severity of hepatitis C induced liver fibrosis. But this does not promote the association between asthma to Korean children or children in Europe and America. rs10399805T alleles associated with elevated IgE in Korean children and allergies (other than asthma), single nucleotide polymorphism and YKL-40 levels in a research about Europeans and Europe and the United States, is a moderate , but relations with allergies have not been repeated. A cross-sectional study of CHI3L1 gene single nucleotide mutation by changing the amount of serum YKL-40 to influence the occurrence of asthma development. But so far, China has not yet reported on CHI3L1 genetic variation associated with asthma and airway hyperresponsiveness. Research Objective To study the gene variation of CH3L1 Chinese asthma patients between detect whether elevated YKL-40 level in the plasma of patients with asthma, while assessing the elevated plasma YKL-40 and the peripheral blood eosinophil and the relationship between lung function. Material and methods collected Nanfang Hospital treatment of patients with bronchial asthma in 260 cases, the diagnosis meet the diagnostic criteria GINA2008 developed asthma, 135 cases of male, female 125 cases; ages 16-77 years old, average (39.5 ± 14.9) years. 272 healthy persons were randomly selected as a control group, these people normal chest X-ray, no cough, sputum and other respiratory symptoms, denied a history of chronic respiratory disease and other respiratory diseases. Allergic rhinitis, asthma medication history, and did not participate in any drug trials; 139 cases of male and female 133 cases; ages 18-81 years old, average (38.87 ± 10.03) years. All subjects were informed consent, extract 4ml peripheral blood spare 2ml of them used to detect blood count, 2ml for genomic DNA extraction and detection of plasma YKL-40 level. The two groups of subjects are Han Chinese, were compared between the two groups object to age, gender, body mass index, there was no significant difference. Asthmatic patients underwent pulmonary function testing, education, disease awareness and prevention episodes of asthma diagnosis and treatment guidelines in accordance with the Chinese Medical Association, the standard medication (90 ± 15) days after the referral, pulmonary function again, and extract 2ml peripheral blood using in plasma YKL-40. Kit to extract the four peripheral blood leukocyte genomic DNA, PCR amplification CHI3L1 gene SNP loci (rs2153101, rs4950928, rs4950929, rs946263), time-of-flight mass spectrometry method to detect single nucleotide polymorphisms. Statistical analysis using SPSS13.0 and SAS software, the basic data used to compare the t-test and X2 test, genetic test of Hardy-Weinberg equilibrium was calculated according to the genetic formula group alleles between allele Armitage trend analysis . The level of YKL-40 does not meet the normal distribution, with median and interquartile range to express, when the first assessment of genetic variation with the YKL-40 in this relationship be the logarithmic transformation, the converted value using Kolmogorov- Smirnov test its normal distribution, and then used for statistical comparisons. Between the two groups YKL-40 was used to compare non-parametric tests. Correlation using Spearman correlation, P lt; 0.05 for the difference was statistically significant. Results between asthma and normal groups age compared using the t-test, t age = -0.763, P = 0.446 2 between asthma and normal groups, gender was used to compare the X2 test, X2 = 0.036, P t test = 0.850. asthma and normal groups used to compare BMI tBMI = -1.599, P = 0.120. 4, asthma and normal groups blood eosinophil percentage of cells (B-EOS%) was used to compare t-test, t = -0.858, P = 0.392. 5, asthma patients plasma YKL-40 levels higher than normal control group (median (interquartile range) 53.50 (32.37-82.36) ng / ml vs34.27 ( 25.62-46.53) ng / ml; Z = -3.911, P = 0.000). 6 different severity of asthma in patients with plasma YKL-40 level difference (X2 = 26.703, P = 0.000). Mild group: 34.22 (24.03-55.48) ng / ml; moderate group: 46.87 (33.31-71.91 ng / ml: severe group: 76.87 (57.41-128.16) ng / ml. 7, pre-treatment plasma YKL-40 FEV1% (r = -0.511, p = 0.000), FEV1/FVC (r = -0.365, p = 0.000), FVC% (r = -0.420, p = 0.000), B-EOS% (r = 0.293, p = 0.001). 8 plasma treatment decreased expression of YKL-40 levels than before treatment (53.50 (32.37-82.36) ng / ml vs43.90 (34.53 to63.28) ng / ml) (Z = -2.171, P = 0.030) The plasma treatment expression of YKL-40 is still with FEV1% (r = -0.298, P = 0.003) and FEV1/FVC (r = -0.244, P = 0.017) and FVC% (r = -0.219 , P = 0.032) correlation exists 10 of CHI3L1 gene rs4950928 G allele was associated with asthma is related to the occurrence (OR, 1.41,95% CI ,1.01-1 .98, X2 = 4.03 P = 0.045). 11, CHI3L1 gene the rs2153101, rs4950929, rs946263 loci not found the incidence of asthma. rs4950928 variation, with GG or CG genotype plasma YKL-40 levels higher than the CC genotype (F = 13.585, P = 0.000 ). 13, rs4950928 G allele in patients with asthma can FEV1% (F = 3.373, P = 0.037), FEV1: FVC (F = 10.708, P = 0.000), but does not reduce FVC% (F = 1.647, P = 0.196). V. Conclusions of CHI3L1 gene rs4950928 single nucleotide polymorphism (SNP) significantly associated with asthma susceptibility in China, C allele may be a protective gene asthma G allele may asthma susceptibility gene. 2, the plasma of patients with asthma expression of YKL-40 levels increased significantly and positively correlated with the severity of the disease, and decreased in the treatment of symptoms improved. prompted YKL-40 can be used as the evaluation of asthma severity. Asthma patients CHI3L1 gene variants affect plasma YKL-40, the level of lung function, the G allele of rs4950928 locus of asthma patients can FEV1%, FEV1/FVC decline, but it does not reduce the FVC% with GG or CG gene type of plasma YKL-40 levels higher than the CC genotype.

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CLC: > Medicine, health > Internal Medicine > Respiratory system and chest diseases > Trachea and bronchial disease > Bronchial disease > Bronchial asthma
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