Single Nucleotide Polymorphism of CYP3A4 Intron 2 and Its Influence on CYP3A4 mRNA Expression and Liver Enzymatic Activity in Human Liver

Summary： In adult liver, CYP3A4 plays an important role in the metabolism of a wide range of en- dogenous and exogenous compounds. To investigate whether there is a single nucleotide polymorphism （SNP） of CYP3A4 intron 2 in the liver and its effects on the mRNA expression and enzymatic activity of CYP3A4, genomic DNA was extracted from 96 liver tissue samples obtained from patients who had undergone liver surgery. An SNP of CYP3A4 intron 2 was identified by polymerase chain reaction （PCR）-single-strand confirmation polymorphism and DNA sequencing. The mRNA expression of CYP3A4 was determined by the fluorescence quantitative PCR technique. The enzymatic activity of CYP3A4 was measured using erythromycin and testosterone as probe substrates. Twelve patients were found to have the SNP/T4127G CYP3A4 within intron 2. The mRNA levels of CYP3A4 in wild-type and SNP/T4127G samples were 2.62±1.09 and 2.79±1.63, respectively （P〉0.05）. Erythromycin N-demethylase activity in wild-type and SNP/T4127G samples were 121.2±32.8 and 124.7±61.6 nmol·mg^-1min^-1, respectively （P〉0.05）. The activity of testosterone 613-hydroxylase was significantly different between wild-type （648±173 pmol·mg^-1·min^-1） and SNP/T4127G samples （540-4-196 pmol.mg-l-minl; P〈0.05）. In conclusion, the SNP/T4127G of CYP3A4 intron 2 exists in the liver. This SNP does not affect the mRNA expression of CYP3A4 but significantly decreases the hepatic micro- somal testosterone 613-hydroxylase activity of CYP3A4. Furthermore, this study indicates that the ap- propriate selection of probe substrates is very important in studying the relationship between the geno- type and phenotype of CYP3A4.

Single nucleotide polymorphisms of MAGE-A3 gene and its clinical implications in Chinese patients with non-small cell lung cancer(NSCLC)

Background： Available study revealed advanced tumors have a higher expression rate of MAGE-A3 gene which has a lot of single nucleotide polymorphism（SNP） loci with polymorphisms. This study aimed to analyze the allele frequency of SNP loci in MAGE-A3 gene and investigate the relationship between MAGE-A3 gene polymorphisms and clinical factors.Methods： Tumor samples of a cohort of 191 NSCLC patients were collected. EGFR m RNA expression were detected by q RT-PCR. SNPs in whole length of MAGE-A3 gene were detected by direct sequencing. Frequencies of the SNPs were correlated to gene expression, mutation status of EGFR and clinical factors.Results： Sequencing analysis confirmed that allele frequencies of genotypes on SNP loci rs5970360, rs5925210, rs5970361, rs5925211 and rs35123853 were CC（0.681）/CT（0.319）, CC（0.660）/CG（0.340）, CC（0.681）/CA（0.319）, AA（0.984）/AT（0.016） and GG（1.000）/GA（0.000）, respectively, which were different from the frequencies and genotypes of MAGE-A3 in SNP database. Chi-square tests showed the EGFR mR NA expression level had significant correlation with the genotypes of SNP loci rs5970360 and rs5925210. But all frequencies of each MAGE-A3 SNPs were not found significantly different between EGFR mutant and wild type patients. MAGE-A3 gene polymorphisms had no significant effects on survival of NSCLC patients.Conclusions： Chinese patients with NSCLC had different SNP patterns of MAGE-A3 in comparison with those in international SNP database. These MAGE-A3 SNP loci might have not prognostic significance. MAGE-A3 SNP loci rs5970360 and rs5925210 might be predictive for EGFR m RNA expression levels and helpful to the selection of patients for epidermal growth factor receptor（EGFR） targeted immunotherapy.

PNPLA3 I148M polymorphism and progressive liver disease

The 148 Isoleucine to Methionine protein variant(I148M)of patatin-like phospholipase domain-containing 3(PNPLA3),a protein is expressed in the liver and is involved in lipid metabolism,has recently been identified as a major determinant of liver fat content.Several studies confirmed that the I148M variant predisposes towards the full spectrum of liver damage associated with fatty liver:from simple steatosis to steatohepatitis and progressive fibrosis.Furthermore,the I148M variant represents a major determinant of progression of alcohol related steatohepatitis to cirrhosis,and to influence fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis,and possibly chronic hepatitis B virus hepatitis,hereditary hemochromatosis and primary sclerosing cholangitis.All in all,studies suggest that the I148M polymorphism may represent a general modifier of fibrogenesis in liver diseases.Remarkably,the effect of the I148M variant on fibrosis was independent of that on hepatic steatosis and inflammation,suggesting that it may affect both the quantity and quality of hepatic lipids and the biology of non-parenchymal liver cells besides hepatocytes,directly promoting fibrogenesis.Therefore,PNPLA3 is a key player in liver disease progression.Assessment of the I148M polymorphism will possibly inform clinical practice in the future,whereas the determination of the effect of the 148M variant will reveal mechanisms involved in hepatic fibrogenesis.

Association between UCP3 gene polymorphisms and nonalcoholic fatty liver disease in Chinese children

AIM:To confirm the hypothesis that polymorphisms of the uncoupling protein 3(UCP3)gene are associated with the occurrence of nonalcoholic fatty liver disease(NAFLD).METHODS:A total of 250 NAFLD patients(147 malesand 103 females)and 200 healthy individuals who served as controls(control,109 males and 91 females),aged between 6 and 16 years were enrolled in this study.The four non-synonymous single nucleotide polymorphisms(SNPs)in the UCP3 gene polymorphisms of rs1726745,rs3781907,rs11235972 and rs1800849,were genotyped using MassArray.Body mass index(BMI),waist and hip circumference,blood pressure(BP),fasting blood glucose(FBG),insulin and lipid profiles were measured and B-ultrasound examination was performed in all subjects.RESULTS:NAFLD patients showed risk factors for metabolic syndrome:elevated BMI,waist-to-hip ratio,BP,FBG,homeostasis model assessment-estimated insulin resistance,total triglyceride,total cholesterol and low-density lipoprotein-cholesterol,while decreased high-density lipoprotein-cholesterol level compared with the control group.The GG genotype distributions of rs11235972 in the NAFLD group differed significantly from that in the control group.We found that waist circumference between CC(58.76±6.45 cm)and CT+TT(57.00±5.59 cm),and hip circumference between CC(71.28±7.84 cm)and CT+TT genotypes(69.06±7.75 cm)were significantly different with and without rs1800849 variation(P<0.05).CONCLUSION:A higher prevalence of rs11235972 GG genotype was observed in the NAFLD group compared with the control group.No differences were observed for the other SNPs.However,there was a significant difference in body height in addition to waist and hip circumference between the CC(mutant type group)and CT+TT group with and without rs1800849 variation.

Lack of association between apolipoprotein C3 gene polymorphisms and risk of nonalcoholic fatty liver disease in a Chinese Han population

AIM: To investigate the association between two polymorphisms of apolipoprotein C3 (APOC3) and risk of nonalcoholic fatty liver disease (NAFLD) in a Chinese Han population.

TCF7L2 rs7903146 polymorphism is associated with gastric cancer: a case-control study in the Venezuelan population

AIM: To explore the association between TCF7L2 rs12255372 and rs7903146 single nucleotide polymorphisms (SNPs) and gastric cancer risk in Venezuelan patients.METHODS: We performed a case-control study including 122 paraffin-embedded archived intestinal-type gastric cancer samples and 129 biopsies obtained by superior endoscopy from chronic gastritis patients. Gastric cancer samples were classified according the degree of carcinoma differentiation. Genomic DNA was extracted from tissues, and the two SNPs of TCF7L2 gene (rs12255372 and rs7903146) were genotyped by polymerase chain reaction-restriction fragment length polymorphism reactions. Multiple regression analysis with adjustments for age and gender were performed and best-fitting models of inheritance were determined. Statistic powers were post-hoc calculated.RESULTS: After adjusting for age and sex the TCF7L2 rs7903146 TT genotype was associated with gastric cancer risk under the recessive genetic model (OR = 3.11, 95%CI: 1.22-7.92, P = 0.017). We further investigated the distribution of rs12255372 and rs7903146 genotypes according gastric cancer stratified by degree of differentiation, and we observed that carriers of rs7903146 T allele (CT + TT vs CC) had a significantly increased risk of moderate/well differentiated gastric cancer (dominant model, OR = 2.55, 95%CI: 1.35-4.80, P = 0.004), whereas the rs7903146 TT genotype was associated with poorly differentiated gastric cancer in the recessive model (OR = 3.65, 95%CI: 1.25-10.62, P = 0.018). We did not find association between rs12255372 SNP and the susceptibility of developing gastric cancer.CONCLUSION: TCF7L2 rs7903146 polymorphism is associated with gastric cancer risk in the Venezuelan population, and could be related to determine the degree of differentiation of tumor cells.

Association of CFH and MAP1LC3B gene polymorphisms with age-related macular degeneration in a high-altitude population

AIM: To evaluate the association of complement factor H(CFH) and microtubule-associated protein 1 light chain 3 beta(MAP1LC3B) gene polymorphisms with the risk of age-related macular degeneration(AMD) in a high-altitude population. METHODS: The study group consisted of 172 participants with symptoms of AMD who were examined and diagnosed between January 2019 and June 2020. The control group was composed of 120 healthy individuals. Each participant was required to provide two milliliters of peripheral blood for DNA extraction. Two single nucleotide polymorphisms(SNPs) of CFH(rs1061170 and rs800292) and two SNPs of MAP1LC3B(rs8044820 and rs9903) were genotyped. The genotypes and allele frequencies of the SNPs in the study and control groups were further compared using Chi-square and Fisher’s exact tests. RESULTS: In a high-altitude population, the nominally significant differences of rs800292 and rs9903’s genotype AG frequencies were observed in the AMD group(P=0.034 and 0.004, respectively). The frequencies of allele G of rs800292 and allele A of rs9903 were also significantly dif ferent in the AMD group compared to the control [(P=0.034, OR=0.70, 95%CI: 0.50-0.98) and(P=0.004, OR=1.60, 95%CI: 1.15-2.22), respectively]. No significant differences in the genotype distributions(P=0.16 and 0.40, respectively) and allele frequencies(P>0.05) of rs1061170 and rs8044820 were observed in the AMD group.CONCLUSION: Genotype AG of rs800292 may be a protective factor for AMD. Conversely, rs9903 seems to be a risk factor for AMD. Therefore, allele G of rs800292 may be a protective factor, and allele A of rs9903, a risk factor for AMD in Qinghai high-altitude population.

CHI3L1基因单核苷酸多态性与儿童哮喘的关联研究

目的探讨几丁质酶3样蛋白1(chitinase 3-like 1,CHI3L1)基因rs4950928、rs883125位点的单核苷酸多态性(single nucleotide polymorphism,SNP)与儿童哮喘易感性、特应性及相关临床指标的关系。方法选取2022年10月—2023年11月就诊于贵州医科大学附属医院儿科的哮喘儿童111例为哮喘组,根据有无过敏性疾病史或过敏原检查阳性分为特应性哮喘组(n=82)和非特应性哮喘组(n=29),另选取同期体检的健康儿童59例为对照组;测定哮喘组儿童外周血总免疫球蛋白E(total immunoglobulin E,tIgE)、呼出气一氧化氮(fractional exhaled nitricoxide,FeNO)及肺功能;采用MassARRAY SNP基因分型技术对两组儿童CHI3L1基因rs4950928、rs883125位点进行基因型检测,Hardy-Weinberg平衡检验基因型频率是否符合遗传平衡。结果rs4950928、rs883125位点哮喘组GC、GG基因型频率、G等位基因频率均高于对照组(P<0.05),rs4950928位点GC基因型患哮喘的风险是CC基因型的2.518倍,G等位基因携带者患哮喘风险分别为C等位基因携带者的2.446倍(P<0.05);rs883125位点GC基因型患哮喘的风险是CC基因型的2.446倍,G等位基因携带者患哮喘风险分别为C等位基因携带者的2.348倍(P<0.05);在非特应性哮喘组和特应性哮喘组之间,rs4950928和rs883125位点的基因型及等位基因分布差异无统计学意义(P>0.05),rs883125位点GC基因型tIgE、FeNO水平高于CC基因型,差异有统计学意义(P<0.05);哮喘儿童rs4950928、rs883125位点不同基因型间肺功能水平差异无统计学意义(P>0.05)。结论CHI3L1基因rs4950928、rs883125是儿童哮喘的易感位点,GC、GG基因型和G等位基因是哮喘的风险因子,rs883125位点SNP与哮喘儿童tIgE、FeNO升高有关、与肺功能水平和哮喘特应性均无关。

CLEC3A gene three polymorphisms and risk of gastric cancer in Northwestern Chinese population

This study aimed to evaluate the association between the CLEC3A gene polymorphisms(rs2735401/rs2293776/rs2072665)and the gastric cancer risk in the Northwestern Chinese population.A hospital-based case-control study was conducted on 681 cases and 756 healthy controls.Odds ratio(OR)and 95%confidence intervals(CI)were applied to evaluate the association of the CLEC3A polymorphisms on gastric cancer risk.We found that there was no significant association between the CLEC3A polymorphisms and gastric cancer susceptibility,which was detected in the main analysis or stratification analyses of age,gender,and clinical stages.Our findings verified that the CLEC3A polymorphisms are not associated with gastric cancer susceptibility in the Northwestern Chinese population;other polymorphisms should be investigated to further clarify the susceptibility to gastric cancer.

Investigation of FOXP3 (rs3761548) polymorphism with the risk of preeclampsia and recurrent spontaneous abortion: A systemic review and meta-analysis

Objective:To investigate the association between forkhead box P3(FOXP3)(rs3761548)polymorphism and the risk of preeclampsia and recurrent spontaneous abortion.Methods:Literature on the association of FOXP3 gene polymorphisms and susceptibility to preeclampsia and unexplained recurrent spontaneous abortion was retrieved by searching databases such as PubMed,Science Direct,Google Scholar and Embase from 2000 to 2021.The association measure was analyzed using an odds ratio(OR)and 95%confidence interval(CI).All the statistical analyses were executed using RevMan 5.4 software.Results:In the present meta-analysis,11 articles were analyzed.The pooled results showed no association between FOXP3 gene polymorphism(rs3761548)and preeclampsia risk in allelic,recessive,dominant and over dominant contrast models.FOXP3 gene polymorphism(rs3761548)showed an association with recurrent abortion in allelic,recessive and dominant models(OR 1.85,CI 1.59-2.14;OR 2.02,95%CI 1.56-2.62;OR 2.69,95%CI 1.50-4.83,respectively),while no association in the over dominant contrast model(OR 1.35,CI 0.87-2.10).Conclusions:In the present study,FOXP3 gene(rs3761548)polymorphism is associated with risk of recurrent spontaneous abortion but not preeclampsia.However,larger sample size and multiracial studies are needed in the future to confirm the findings.

Foxp3 rs2294021 polymorphism contributes to the susceptibility to breast carcinoma

Objective:Foxp3,the main regulator of Treg (regulatory T) cells, is down-regulated in breast carcinoma and other cancers. The rs2294021 Foxp3 polymorphism contributes to Foxp3 down-regulation, thereby weakens its tumor suppressing activity. The aim of our study was to evaluate the potential influence of Foxp3 polymorphism on breast cancer, we conducted a case-control study in Han Chinese women. Methods: Foxp3 genotyping was conducted in 677 breast carcinoma patients and 828 age-frequency matched cancer-free controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Experiment data was analyzed using Chi-square test and SPSS software. Results: The T/C genotype was found to be significantly associated with increased risk of breast carcinoma occurrence (OR = 1.462; 95% CI 1.165-1.833, P = 0.001) compared with the T/T or C/C (OR 1.143; 95% CI 0.838-1.559, P = 0.397) genotype. The increased risk for breast carcinoma related to heterozygous genotype was more pronounced in subjects over 50 years (OR 1.631; 95% CI 1.116-2.383, P = 0.011). No significant association was found between the polymorphism and the ER/PR status, metastasis or tumor stage of breast cancer. Conclusion: Our findings suggest that rs2294021 Foxp3 polymorphism may be a potential contributor for development of breast carcinoma in Han Chinese women.

Single Nucleotide Polymorphism rs10919543 in FCGR2A/ FCGR3A Region Confers Susceptibility to Takayasu Arteritis in Chinese Population

Background： Takayasu arteritis （TA） is a rare inflammatory arteriopathy of unknown etiology. The aim of this study was to investigate the genetic susceptibility to TA in a Chinese population. Methods： Four single nucleotide polymorphisms （SNPs） those locate in the IL12B region （rs56167332）, the MLX region （rs665268）, the FCGR2A/FCGR3A locus （rsi0919543）, and the HLA-B/M1CA locus （rs12524487）, associated with TA in different population, were genotyped in 123 Chinese TA patients and 147 healthy controls from January 2013 to August 2014. A Chi-square test was used to test for genotype/allele frequencies variants. Results： Among the four SNPs, rs 10919543 was found to be significantly associated with TA in the studied population. The GG genotype of rs 10919543 at the FCGR2A/FCGR3A locus is a high risk factor （odds ratio [OR] = 6.532, 95% confidence interval [C1] = 2.402 - 17.763, P 〈 0.001 ） for TA. Among TA patients, the level of eosinophil granulocytes （Eos） in the peripheral blood was observed to be higher in the GG group of rs 10919543 （n = 23, Eos = 0. I 1 [0.08, 0.17] x 109/L） than the GA ＋ AA group （n = 100, Eos = 0.08 [0.05, 0.13] 10/L, P = 0.028）. No correlation between the genotypes of the other three SNPs and TA patients was observed. Conclusions： Our findings revealed unique genetic pattern in Chinese TA patients that may be partly responsible for the higher risk of TA in this population. FCGR2A/FCGR3A-related immune disorder might contribute to the etiology of TA.

小核RNA激活复合体多肽3基因rs4741506多态性与中国汉族人群缺血性脑卒中及其中医证候的相关性分析

目的探讨中国汉族人群中小核RNA激活复合体多肽3(SNAPC3)基因rs4741506多态性与缺血性脑卒中(IS)及其中医证候的关系。方法选取2016年1月至2019年12月在广西中医药大学第一附属医院脑病科住院治疗的774例IS患者作为观察组,同期本院体检中心的健康体检者以及医院骨科轻症外伤患者793例作为对照组。对IS患者进行中医证候辨证,对SNAPC3基因多态性位点rs4741506进行基因分型检测。建立4种遗传模型,应用PLINK软件和SPSS 21.0软件进行遗传关联及基因位点多态性与IS及其中医证候和患者临床指标的相关性分析。结果观察组与对照组rs4741506位点的基因型频率分布差异有统计学意义(χ^(2)=6.366,P=0.041)。在加性模型、显性模型、隐性模型中,SNAPC3基因rs4741506多态性与IS的发生风险均无显著相关性(均P>0.05)。多因素Logistic回归模型分析结果显示,校正年龄和性别后SNAPC3基因rs4741506多态性与IS风证(隐性模型:比值比=0.45,95%置信区间:0.22~0.92,P=0.029)、痰证(隐性模型:比值比=0.39,95%置信区间:0.19~0.81,P=0.011)发生风险相关,而与血瘀证的发生风险无明显相关性(显性模型:比值比=1.42,95%置信区间:1.00~2.01,P=0.051)。在隐性模型下,校正年龄和性别后SNAPC3基因rs4741506多态性与IS痰证患者舒张压水平相关(β=-10.93,95%置信区间:-20.64~-1.22,P=0.028)。一般线性回归分析结果显示,校正年龄和性别后SNAPC3基因rs4741506多态性与IS痰证患者血清载脂蛋白A1(加性模型、显性模型)、载脂蛋白B(隐性模型)、血小板计数(加性模型、显性模型)水平、凝血酶时间(显性模型)显著相关(均P<0.05)。结论SNAPC3基因rs4741506多态性可能影响IS风证及痰证的发生发展。

Role of genetic polymorphisms in hepatitis C virus chronic infection

AIM: To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C(CHC).METHODS: We conducted an electronic search on the Pub Med and MEDLINE(2000-2014) databases and Cochrane library(2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article.RESULTS: Several studies associated polymorphisms in the interleukin 28 B gene on chromosome 19(19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon(PegIFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC patients. Although not conclusive, some investigations suggested that the vitamin D-associated polymorphisms play an important role in the achievement of sustained virologic response in CHC patients treated with Peg-IFN-based antiviral therapy. Several other polymorphisms have been investigated to ascertain their possible impact on the natural history and on the response to treatment in patients with CHC, but the data are preliminary and warrant confirmation. CONCLUSION: Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies.

Promoting genetics in non-alcoholic fatty liver disease: Combined risk score through polymorphisms and clinical variables

Non-alcoholic fatty liver disease(NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma(HCC). Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis. The rs738409 single nucleotide polymorphism(SNP) in patatin-like phospholipase domain-containing protein 3 gene and the rs58542926 SNP in transmembrane 6 superfamily member 2 gene have been robustly associated with NAFLD and with its progression, but promising results have been obtained with many other SNPs. Moreover, there has been proof of the additive role of the different SNPs in determining liver damage, and there have been preliminary experiences in which risk scores created through a few genetic variants, alone or in combination with clinical variables, were associated with a strongly potentiated risk of NAFLD, non-alcoholic steatohepatitis(NASH), NASH fibrosis or NAFLD-HCC. However, to date, clinical translation of genetics in the field of NAFLD has been poor or absent. Fortunately, the research we have done seems to have placed us on the right path: We should rely on longitudinal rather than on cross-sectional studies; we should focus on relevant outcomes rather than on simple liver fat accumulation; and we should put together the genetic and clinical information. The hope is that combined genetic/clinical scores, derived from longitudinal studies and built on a few strong genetic variants and relevant clinical variables, will reach a significant predictive power, such as to have clinical utility for risk stratification at the single patient level and even to esteem the impact of intervention on the risk of disease-related outcomes. Well-structured future studies would demonstrate if this vision can become a reality.

哮喘儿童ORMDL3基因多态性及基因与环境交互作用的分析

目的 研究血清类黏蛋白1样蛋白3(ORMDL3)基因rs7216389、rs12603332位点单核苷酸多态性(SNP)及该基因-环境交互作用与儿童哮喘的关系。方法 选取102例哮喘儿童为哮喘组、54例健康儿童为对照组,分别比较两组儿童ORMDL3基因rs7216389、rs12603332位点的等位基因及基因型频率差异;采用logistic回归分析ORMDL3基因与儿童哮喘患病风险的关系,Haploview软件进行连锁不平衡及单倍型分析,广义多因子降维法(GMDR)分析ORMDL3基因与环境的交互作用。结果 ORMDL3基因rs7216389位点哮喘组TT、TC基因型频率均高于对照组(P<0.05),等位基因频率在两组间分布差异无统计学意义(P>0.05),rs12603332等位基因及基因型频率在两组分布均差异无统计学意义(P>0.05);rs7216389位点TT和TC基因型儿童哮喘患病风险分别为CC基因型儿童的7.000倍和8.312倍(P<0.05);rs12603332位点AG基因型儿童哮喘患病风险为AA基因型儿童的4.266倍(P<0.05);两位点显示强连锁不平衡(D=1),单倍型TG、CA、TA在两组间分布差异均无统计学意义(P>0.05);GMDR显示两位点存在交互作用(P<0.05),rs7216389位点与湿疹史、家族过敏史、特应性存在交互作用(P<0.05)。结论 ORMDL3基因rs7216389、rs12603332位点基因多态性与儿童哮喘患病风险有关,两位点间及rs7216389位点与湿疹史、家族过敏史、特应性具有交互作用。

TLR3基因单核苷酸多态性与儿童紫癜性肾炎的相关性

目的探讨TLR3基因单核苷酸多态性与儿童过敏性紫癜(Henoch-Schönlein purpura,HSP)及紫癜性肾炎(Henoch-Sch nleinöpurpura nephritis,HSPN)易感性的相关性。方法选择HSP患儿174例作为病例组,选择同期体检的162例健康儿童作为对照组。根据病例组患儿在随访过程中是否合并肾脏损害分为HSP组、HSPN组。采用多重聚合酶链反应技术(M-PCR)靶向捕获TLR3基因rs35311343、rs121434431、rs199768900、rs768091235、rs1244010954位点,通过高通量测序技术对所有样本的上述位点进行测序,根据测序结果进行各位点基因型以及基因频率的统计分析。结果病例组与对照组TLR3基因rs35311343、rs121434431、rs199768900、rs768091235、rs1244010954位点的各基因型频率和各等位基因频率比较,差异无显著意义(P>0.05)。病例组中HSP组与HSPN组TLR3基因rs121434431、rs199768900、rs768091235、rs1244010954位点的各基因型频率和各等位基因频率比较,差异无显著性(P>0.05);rs35311343位点的基因型频率与等位基因频率比较差异有显著性(χ^(2)=9.492,OR=2.662,95%CI=1.342~5.281,P<0.05)。结论TLR3基因rs35311343位点CG基因型与儿童过敏性紫癜肾脏受累有关,等位基因G可能是HSPN的易感基因。

Single nucleotide polymorphism rs11191454 in arsenite methyltransferase is associated with flow in Chinese students:a genetic study on flow experience

Flow has been widely studied in the field of positive psychology.However,little is known regarding its biological mechanism.This study aimed to ascertain flow-related gene loci.We investigated the association between flow and five single nucleotide polymorphisms associated with common mental disorders among a sample of 870 healthy 1 st year students of Jining Medical University,Shandong Province,China.This study was approved by the Ethics Committee of Jining Medical University(approval number:JNMC-2016-KY-001)on June 1,2016.rs11191454 demonstrated significant statistical association with flow after adjusting for age and gender(P=0.004).The allele carriers achieved higher scores in all 4 dimensions of flow:merging of action and awareness,challenge-skill balance,sense of control,and clear goals.This biological research article indicates that rs11191454 in the arsenite methyltransferase(AS3MT)gene might be associated with flow in a Chinese Han population,and that might result from altered arsenic metabolism.

自身免疫性肝病患者SH2B3基因Rs3184504单核苷酸多态性分析

目的探讨自身免疫性肝病(AILD)患者SH2B衔接蛋白3(SH2B3)基因中Rs3184504单核苷酸多态性(SNP)变化。方法2017年6月~2023年10月我院收治的58例自身免疫性肝炎(AIH)、62例原发性胆汁性胆管炎(PBC)患者和同期体检的60例健康人,采用PCR法检测SH2B3基因中Rs3184504位点多态性。应用Logistic回归分析SH2B3基因Rs3184504单核苷酸多态性与AIH或PBC的患病风险度。结果AIH组SH2B3基因Rs3184504位点中TT基因型和等位基因T占比分别为53.4%和66.4%,PBC组分别为54.8%和69.4%,均显著高于健康人(分别为16.7%和26.7%,P<0.05),而AIH组和PBC组SH2B3基因Rs3184504位点中CC基因型分别为20.7%和16.1%,均显著低于健康人的63.3%(P<0.05);Logistic回归分析显示,相对于SH2B3基因Rs3184504位点中CC基因型携带者,TT基因型携带者AIH患病风险提高了2.529倍(OR=2.529,P<0.05),相对于SH2B3基因Rs3184504位点中CC基因型携带者,CT基因型携带者PBC患病风险提高了2.812倍(OR=2.812,P<0.05),TT基因型携带者PBC患病风险提高了2.370倍(OR=2.370,P<0.05)。结论AILD与SH2B3基因中Rs3184504单核苷酸多态性变化有关,其中TT基因是AIH易感基因型,CT和TT基因型是PBC易感基因型,携带T等位基因的患者发生AILD的风险增加。

CHI3L1基因多态性和血清YKL-40水平与支气管哮喘发病的关联性

目的：观察几丁质酶3类1（CHI3L1）基因多态性与广东地区汉族人群哮喘发病的关联性，探讨采用其编码的几丁质酶样蛋白40（YKL-40）评估病情严重程度及监测病情的临床意义。方法：入选的251例研究对象分为哮喘组（150例）和正常对照组（101例）。采用 Massarray法检测 CHI3L1基因单核苷酸多态性（SNP），同时检测哮喘组和对照组研究对象血清 YKL-40水平、外周血嗜酸性粒细胞百分比（Eos％）、总 IgE和肺功能，同时将哮喘组分为急性加重期和稳定期2个亚组，比较患者血清 YKL-40水平的差异。结果：CHI3L1基因位点rs3806448 A/G等位基因在哮喘组和对照组中分布比较差异有统计学意义（P＜0.01），哮喘组患者 rs3806448等位基因 A频数明显高于正常对照组（OR＝1.93，95％CI＝1.30～2.62，χ2＝11.6，P＜0.01）；rs3806448基因型为AA患者血清YKL-40水平、总IgE和Eos％高于基因型为GG或AG患者（P＜0.05）；而rs3806448基因型为AA患者一秒用力呼气容积（FEV1）占预计值百分比（FEV1％）低于基因型为 GG或 AG患者（P＜0.05）；哮喘组患者血清YKL-40水平明显高于正常对照组（P＜0.01），哮喘急性加重组患者血清 YKL-40水平高于病情稳定组和正常对照组（P＜0.01）；哮喘组患者血清 YKL-40水平与外周血 EOS％及总 IgE 水平呈正相关关系（rEos＝0.348，rIgE＝0.437，P＜0.01），与肺功能呈负相关关系（r＝-0.745，P＜0.01）。结论：CHI3L1-rs3806448多态性与广东地区汉族人群的哮喘发病有关联，提示血清 YKL-40可能是评价哮喘患者病情严重程度及监测病情变化的一个新生物标志物。