葡萄糖转运体9(GLUT9)基因启动子区的rs13124007(G/C)及rs6850166(G/A)位点的单核苷酸多态性(SNP)与汉族女性痛风相关性研究

目的:探讨葡萄糖转运体9(GLUT9)基因启动子区的rs13124007(C/G)及rs6850166(A/G)位点的单核苷酸多态性(SNP)与中国汉族女性人群痛风易感性之间的相关性.方法:选取185例痛风患者和300例正常对照者,提取基因组DNA,采用聚合酶链式反应(PCR技术),特异性扩增GLUT9基因所需要的目的片段,对扩增的目的片段进行测序后,比较痛风组和正常对照组的基因型频率及等位基因频率分布情况.结果:女性痛风组中GLUT9基因的启动子区rs13124007和rs6805116两个位点的基因型频率分布与正常对照组相比,统计学上无明显的差异(X2=0.906,P=0.636;X2=3.335,P=0.189),rs13124007 SNP位点的C等位基因频率和rs6850166SNP位点的A的等位基因频率与正常对照组相比也无明显的统计学差异(X2=0.506,P=0.477;X=3.268,P=0.071).结论:葡萄糖转运体9(GLUT9)基因启动子区的rs 13124007(C/G)及rs6850166(A/G)位点的单核苷酸多态性(SNP)与中国汉族女性人群痛风易感性无明显的相关性.     

Association of interleukin-13 SNP rs1800925 with allergic rhinitis risk: A meta-analysis based on 1,411 cases and 3169 controls

Studies investigating the association between interleukin-13 (IL-13) single nucleotide polymorphism (SNP) rs1800925 and allergic rhinitis risk have reported conflicting results. The aim of the present study was to conduct a meta-analysis assessing the possible association of IL-13 SNP rs1800925 with allergic rhinitis risk. The relevant studies were identified through a search of PubMed, Embase, ISI Web of Knowledge and Chinese National Knowledge Infrastructure until December 2011 and selected on the basis of the established inclusion criteria for publications. Five studies were included in the present meta-analysis (1411 cases and 3169 controls). The combined results based on all studies showed that IL-13 SNP rs1800925 was not associated with increased allergic rhinitis risk (T versus C: odds ratio (OR)=1.06, 95% confidence interval (CI)=0.94-1.20; C/T versus C/C: OR=1.12, 95% CI=0.97-1.29; T/T versus C/C: OR=1.00, 95% CI=0.69-1.44; C/T+T/T versus CC: OR=1.10, 95% CI=0.96-1.27; T/T versus C/C+C/T: OR=0.91, 95% CI=0.64-1.31). This meta-analysis supported that IL-13 SNP rs1800925 was not associated with allergic rhinitis.     

中国汉族人群中RELN基因rs7341475位点与精神分裂症的相关性分析

精神分裂症是一种常见的复杂精神疾病.大量的实验证据表明,遗传因素在精神分裂症的发生中起到了重要的作用.截至目前,有报道称至少100个基因与精神分裂症相关,但它们在不同人群中的重复性不好.在这些基因中,RELN在多个人群中都被证实与精神分裂症相关,表明它可能是一个真实的易感基因.目前,在RELN基因上有很多个单核苷酸多态性位点被证实与精神分裂症相关,其中研究最多的是通过全基因组关联分析发现的在RELN基因第四个内含子中的单核苷酸多态性位点rs7341475,它被证明与精神分裂症的发生相关.为了验证该位点在中国人群中是否与精神分裂症相关,作者对来自中国玉溪的病例——对照样本(400位患者和400位正常人)进行了遗传分析.结果显示,在该样本中rs7341475与精神分裂症不相关,这表明rs7341475在中国人群中可能不是致病多态性位点.     

Impact of Comorbidities on Mortality in Patients with Idiopathic Pulmonary Fibrosis

Introduction

Comorbidities significantly influence the clinical course of idiopathic pulmonary fibrosis (IPF). However, their prognostic impact is not fully understood. We therefore aimed to determine the impact of comorbidities, as individual and as whole, on survival in IPF.

Methods

The database of a tertiary referral centre for interstitial lung diseases was reviewed for comorbidities, their treatments, their frequency and survival in IPF patients.

Results

272 patients were identified of which 12% had no, 58% 1–3 and 30% 4–7 comorbidities, mainly cardiovascular, pulmonary and oncologic comorbidities. Median survival according to the frequency of comorbidities differed significantly with 66 months for patients without comorbidities, 48 months when 1–3 comorbidities were reported and 35 months when 4–7 comorbidities were prevalent (p = 0.004). A multivariate Cox proportional hazard analyses identified other cardiac diseases and lung cancer as significant predictors of death, gastro-oesophageal reflux disease (GERD) and diastolic dysfunction had a significant positive impact on survival. A significant impact of comorbidities associated therapies on survival was not discovered. This included the use of proton pump inhibitors at baseline, which was not associated with a survival benefit (p = 0.718). We also established a predictive tool for highly prevalent comorbidities, termed IPF comorbidome which demonstrates a new relationship of IPF and comorbidities.

Conclusion

Comorbidities are frequent in IPF patients. Some comorbidities, especially lung cancer, mainly influence survival in IPF, while others such as GERD may inherit a more favourable effect. Moreover, their cumulative incidence impacts survival.     

Association of Interleukin-13 SNP rs20541 (Arg > Gln) to allergic rhinitis in an Asian population of ethnic Chinese in Singapore

In this study, we report our findings as we evaluated the association of IL-13 SNP rs20541 to AR as reported in the meta-analysis (Ying, X-J et al., April, Gene 2013) in an Asian population of 1322 ethnic Chinese recruited in Singapore well defined and characterized for allergic rhinitis. The SNP was significantly associated with AR at an odds ratio of 1.57 for the homozygous genotype comparisons indicating a strong risk for AR. This highlights the importance of this mutation in Asian populations for risk towards allergic phenotypes and also warrants further functional work to characterize the mechanism behind this genetic predisposition.     

rs2200733多态性与中国汉族中青年高血压患者并发心房颤动的关联性

目的:探讨人基因组rs2200733位点的多态性与中国汉族中青年高血压患者并发房颤发生的关联性.方法:根据入选标准,选择中国汉族中青年高血压并发房颤患者208例(房颤组)和不伴房颤的高血压患者405例(对照组).采集患者外周血,提取基因组DNA,采用聚合酶链反应-限制性酶切片段长度多态性技术检测rs2200733位点的基因型和等位基因分布.结果:rs2200733位点存在多态性,分别为TT、TC和CC型,其基因型频率在房颤组和对照组分别为58.1％、33.7％、8.2％和72.9％、25.9％、1.2％.基因型分布有显著性差异(P＜0.001),房颤组TC和CC基因型频率明显高于对照组(P＜0.001).Logistic多因素回归分析显示rs2200733位点多态性与房颤显著相关(OR=3.143,95％CI:1.442-6.581).结论:rs2200733位点多态性与中国汉族中青年高血压患者的房颤发生存在相关性,TC和CC基因型可能是房颤发生的一个遗传易感因素.     

Interleukin-28B rs12979860C/T and rs8099917T/G contribute to spontaneous clearance of hepatitis C virus in Caucasians

Two single nucleotide polymorphisms rs12979860C/T and rs8099917T/G around interleukin-28B (IL28B) locus have been extensively investigated in their association with hepatitis C virus (HCV) spontaneous clearance. However, with the variable and even inconsistent results, it is necessary to conduct a meta-analysis. A literature search was conducted to seek articles about genetic variation of IL28B and spontaneous clearance of HCV. Odds ratio with 95% confidential interval were calculated to estimate their relationship. Furthermore, meta-regression analysis was performed to search for potential affective factors. A total of 8 studies including 2460 patients with chronic HCV infection and 1052 individuals with spontaneous HCV clearance met inclusion criteria, in which seven studies describing rs12979860 and three studies describing rs8099917. Analysis performed in Caucasian populations indicated that rs12979860CC and rs8099917TT contributed to HCV spontaneous clearance in both dominant model (CC vs. CT + TT, P < 1 × 10^− 4; TT vs. TG + GG, P < 10^− 4, respectively) and co-dominant model (CC vs. CT, P < 1 × 10^− 4, CC vs. TT, P < 1 × 10^− 4; TT vs. TG, P < 10^− 4, TT vs. GG, P = 0.012, respectively). Meta-regression analysis suggested that male proportion (P = 1 × 10^− 5) and mean age (P = 1 × 10^− 3) might weaken the effect of rs12979860CC, but HCV genotype 1/4 (P = 4 × 10^− 4) might contribute to it. IL28B rs12979860CC and rs8099917TT genotypes contribute to spontaneous HCV clearance in Caucasians.     

Association of interleukin-13 SNP rs20541 with allergic rhinitis risk: A meta-analysis

Studies investigating the association between interleukin-13 (IL-13) single nucleotide polymorphism (SNP) rs20541 and allergic rhinitis (AR) risk have reported conflicting results. The aim of the present study was to conduct a meta-analysis assessing the possible association of IL-13 SNP rs20541 with AR risk. Eight studies were included in the present meta-analysis (2153 cases and 3931 controls). The combined results based on all studies showed that IL-13 SNP rs20541 was associated with increased AR risk (Gln versus Arg: odds ratio (OR) = 1.18, 95% confidence interval (CI) = 1.08–1.30; Gln/Gln versus Arg/Arg: OR = 1.52, 95% CI = 1.20–1.92; Arg/Gln + Gln/Gln versus Arg/Arg: OR = 1.19, 95% CI = 1.06–1.33; Gln/Gln versus Arg/Gln + Arg/Arg: OR = 1.42, 95% CI = 1.13–1.79). When stratifying for race, IL-13 SNP rs20541 exhibited increased AR risk in Asians (Gln versus Arg: OR = 1.20, 95% CI = 1.06–1.36; Gln/Gln versus Arg/Arg: OR = 1.57, 95% CI = 1.17–2.12; Arg/Gln + Gln/Gln versus Arg/Arg: OR = 1.22, 95% CI = 1.04–1.44; Gln/Gln versus Arg/Gln + Arg/Arg: OR = 1.45, 95% CI = 1.09–1.93), while no significant association was detected in Caucasians (Gln versus Arg: OR = 1.28, 95% CI = 0.93 ~ 1.78; Gln/Gln versus Arg/Arg: OR = 1.42, 95% CI = 0.96–2.11; Arg/Gln + Gln/Gln versus Arg/Arg: OR = 1.35, 95% CI = 0.89–2.05; Gln/Gln versus Arg/Gln + Arg/Arg: OR = 1.37, 95% CI = 0.93–2.02). This meta-analysis supported that IL-13 SNP rs20541 was associated with AR, particularly in Asians.     

The Association of Adiponectin Gene Promoter Variations with Non-Small Cell Lung Cancer in a Han Chinese Population

Recently, in vitro studies have demonstrated that adiponectin has antiangiogenic and tumor growth-limiting properties. Additionally, serum adiponectin levels have been associated with the risk of several cancers; specifically, serum adiponectin was significantly lower in lung cancer patients with advanced-stage disease. In this study, we examined the association of adiponectin gene promoter variations associated with adiponectin gene expression and plasma levels in non-small cell lung cancer (NSCLC) in a Han Chinese population. A total of 319 patients with NSCLC and 489 healthy individuals were recruited to evaluate the association of four adiponectin gene promoter single-nucleotide polymorphisms (SNPs) (SNP-12140G>A, SNP-11426A>G, SNP-11391G>A and SNP-11377C>G) with NSCLS risk. Additionally, we constructed haplotypes of these four SNPs and evaluated the association of these haplotypes with NSCLS risk. Our results showed that among these four SNPs, only SNP-12140G>A was associated with NSCLC risk(P<0.05). The haplotype analysis showed that no haplotype was associated with NSCLC after performing a Bonferroni correction (P>0.05). Additionally, an association analysis of the four SNPs stratified into pathologic stages I+II and III+IV showed that these SNPs did not exhibit significant differences between pathologic stages I+II and III+IV. Moreover, we did not observe any differences in allele and genotype frequency for these SNPs between adenocarcinoma and squamous cell carcinoma. Our results indicated that the G allele of SNP-12140may be a risk factor for NSCLC (OR = 1.516; 95% CI: 1.098–2.094) in this Han Chinese population.     

Alterations in Adenosine Metabolism and Signaling in Patients with Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis

Background

Adenosine is generated in response to cellular stress and damage and is elevated in the lungs of patients with chronic lung disease. Adenosine signaling through its cell surface receptors serves as an amplifier of chronic lung disorders, suggesting adenosine-based therapeutics may be beneficial in the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Previous studies in mouse models of chronic lung disease demonstrate that the key components of adenosine metabolism and signaling are altered. Changes include an up-regulation of CD73, the major enzyme of adenosine production and down-regulation of adenosine deaminase (ADA), the major enzyme for adenosine metabolism. In addition, adenosine receptors are elevated.

Methodology/Principal Findings

The focus of this study was to utilize tissues from patients with COPD or IPF to examine whether changes in purinergic metabolism and signaling occur in human disease. Results demonstrate that the levels of CD73 and A_2BR are elevated in surgical lung biopsies from severe COPD and IPF patients. Immunolocalization assays revealed abundant expression of CD73 and the A_2BR in alternatively activated macrophages in both COPD and IPF samples. In addition, mediators that are regulated by the A_2BR, such as IL-6, IL-8 and osteopontin were elevated in these samples and activation of the A_2BR on cells isolated from the airways of COPD and IPF patients was shown to directly induce the production of these mediators.

Conclusions/Significance

These findings suggest that components of adenosine metabolism and signaling are altered in a manner that promotes adenosine production and signaling in the lungs of patients with COPD and IPF, and provide proof of concept information that these disorders may benefit from adenosine-based therapeutics. Furthermore, this study provides the first evidence that A_2BR signaling can promote the production of inflammatory and fibrotic mediators in patients with these disorders.     

白介素18启动子区基因多态性与儿童EV71感染相关性研究

目的:研究白介素18基因启动子多态性与儿童EV71感染遗传易感性的关系.方法:收集EV71感染患儿177例,单纯HFMD组127例,HFMD并脑炎组50例,提取外周血DNA,用序列特异性引物-聚合酶链反应(SSP-PCR)技术及基因测序法检测IL-18启动子区-137G/C、-607A/C位点的基因多态性.结果:EV71感染患儿与健康儿童IL-18-607基因型以CA为主,AA、CC次之,EV71感染患儿AA基因型、A等位基因分布频率显著高于健康儿童.EV71感染HFMD并脑炎组患儿AA基因型分布显著高于单纯HFMD组患儿,差异有统计学意义.EV71感染患儿与健康儿童IL-18-137基因型以CC为主,CG次之,GG占少数.该位点基因型及等位基因在EV71感染组与健康儿童、单纯HFMD与HFMD并脑炎组的分布无显著差异.结论:IL-18基因多态性与EV71感染相关,IL-18-607AA基因型、A等位基因携带儿童更易感染EV71病毒,且AA基因型患儿易并发脑炎,-607AA基因型可能为EV71感染的易感基因型.-137C/G位点基因多态性与EV71感染无相关性.     

白介素10和白介素17基因启动子区多态性位点与儿童哮喘 的相关性研究

目的:探讨IL-10基因启动子区-627A/C和IL-17基因启动子-152A/G位点多态性与儿童哮喘发生的相关性。方法:采用聚合酶链反应-限制性片段长度多态性分析(PCR-PFLP)方法检测186名哮喘儿童、198名健康儿童各个多态性位点的基因型,采用SPSS13.0进行统计学分析。结果:IL-17基因-152A/G位点的基因型及等位基因频率分布在哮喘组与正常对照组均存在显著性差异(p<0.05),哮喘组-152A/G位点等位基因A频率显著高于正常对照组(x2=6.077,p=0.014,OR=1.430,95%CI=1.076-1.902)。结论:IL-17基因-152A/G位点可能与儿童哮喘的发病存在关系,其中A等位基因可能是易感基因,携带A的个体可能更易患有哮喘。     

Association between Polymorphism of the Interleukin-13 Gene and Susceptibility to Hepatocellular Carcinoma in the Chinese Population

ObjectiveInterleukin-13 (IL-13) is a potent pleiotropic cytokine that is produced by activated CD4 T cells. This study was undertaken to determine the relationship between two IL-13 gene single nucleotide polymorphisms (SNP rs1800925 and SNP rs20541) and the incidence of hepatitis B virus-related (HBV) hepatocellular carcinoma (HCC).MethodThree hundred and ninety-eight HBV-positive individuals (192 HCC and 206 patients with chronic hepatitis) and one hundred and ninety-two healthy participants from the First Affiliated Hospital of Guangxi Medical University were enrolled in this study.ResultsThe results showed no significant differences between the genotype and allele frequencies of the IL-13 gene rs1800925 and rs20541 polymorphisms and chronic hepatitis B risk after adjusting for age, sex, tobacco use, and alcohol intake using binary logistic regression analyses. Regarding the rs20541 SNP, the GA genotype was significantly related to a decreased risk of HCC after adjusting for age, sex, tobacco use, and alcohol intake using binary logistic regression analyses (The odds ratio (OR) = 0.54, 95% confidence intervals (CI) 0.34–0.87). The adjusted OR for the GA and AA genotypes combined was 0.68 (95% CI 0.39–0.90).ConclusionThis study indicates that the functional IL-13 rs20541 polymorphism may contribute to the risk of HCC and that the rs20541 polymorphism is a protective factor for HCC.     

SNP rs2243828 in MPO associated with myeloperoxidase level and atrial fibrillation risk in Chinese Han population

Previous studies shown that myeloperoxidase (MPO) level is higher in patients with atrial fibrillation (AF); however, no genetic evidence between MPO and AF risk in human population was observed. Therefore, the present study was aimed to investigate the association between rs2243828, a variant in promoter region of MPO and the risk of AF in Chinese GeneID population. The results demonstrated that the minor G allele of rs2243828 showed a significant association with AF in two independent population (GeneID‐north population with 694 AF cases and 710 controls, adjusted P_‐adj = 6.25 × 10^?3 with an odds ratio was 0.77, GeneID‐central population with 1106 cases and 1501 controls, P_‐adj = 9.88 × 10^?5 with an odds ratio was 0.75). The results also showed G allele was significantly associated with lower plasma concentration of myeloperoxidase in general population. We also observed a significant difference of odds ratio between subgroups of hypertension and non‐hypertension. Therefore, our findings identified variant in MPO associated with risk of AF and it may give strong evidence to link the inflammation with the incidence of AF.     

Promoter Polymorphism in the Serotonin Transporter (5-HTT) Gene Is Significantly Associated with Leukocyte Telomere Length in Han Chinese

The serotonin transporter gene (5-HTT)-linked polymorphic region (5-HTTLPR) plays an important role in modulating mood and behavior by regulating 5-HTT expression and thereby controlling the concentration of serotonin (5-HT) in brain synapses: The homozygous shorter allele (S/S) in 5-HTTLPR results in lower 5-HTT expression coupled with stronger psycho-pathological reactions to stressful experiences compared to the homozygous long (L/L) and heterozygous (S/L) alleles. Psychological insults and mood disorders have been shown to cause accelerated telomere shortening, a marker of biological aging, however, it is currently unclear whether the allelic variants of 5-HTTLPR affect telomere length (TL) in the healthy population without mood disorders. In the present study, we determined the relationship between TL and the 5-HTTLPR variants in healthy Han Chinese. The 5-HTTLPR genotyping and leukocyte TL analysis of 280 young female Han Chinese freshmen showed a significantly shorter TL in 149 of them carrying the 5-HTTLPR S/S version compared to those (131) with the L/S or L/S plus L/L genotypes (mean ± SD, 0.533±0.241 for S/S vs 0.607±0.312 for L/S, P  =  0.034; or vs 0.604±0.313 for L/S plus L/L, P  =  0.038). Similar results were achieved in the other cohort including 220 adult healthy individuals of different age, gender and profession (0.691±0.168 for S/S vs 0.729±0.211 for L/S, P  =  0.046, or vs 0.725±0.213 for L/S plus L/L, P  =  0.039). Taken together, shorter leukocyte TL is significantly associated with the 5-HTTLPR S/S allelic variant, which may be implicated in psychological stress-related health problems.     

Association of C3435T (rs1045642) Polymorphism of the MDR1 Gene with the Increased Risk of Colorectal Cancer in Russian Females from Central Russia

Russian Journal of Genetics - The objective of this study was to examine associations of single nucleotide polymorphisms, rs1045642 within the MDR1 gene and rs1799930 within the NAT2 gene, with the...     

Significant association of SNP rs2106261 in the ZFHX3 gene with atrial fibrillation in a Chinese Han GeneID population

Atrial fibrillation (AF) is the most common cardiac rhythm disorder at the clinical setting and accounts for up to 15% of all strokes. Recent genome-wide association studies (GWAS) identified two single nucleotide polymorphisms (SNPs), rs2106261 and rs7193343 in ZFHX3 (zinc finger homeobox 3 gene) and rs13376333 in KCNN3 (encoding a potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3) that showed significant association with AF in multiple populations of European ancestry. Here, we studied a Chinese Han, GeneID cohort consisting of 650 AF patients and 1,447 non-AF controls to test whether the GWAS findings on ZFHX3/KCNN3 and AF can be expanded to a different ethnic population. No significant association was detected for rs7193343 in ZFHX3 and rs13376333 in KCNN3. However, significant association was identified between rs2106261 in ZFHX3 and AF in the GeneID population for both allelic frequencies (P=0.001 after adjusting for covariates of age, gender, hypertension, coronary artery disease, and diabetes mellitus; OR=1.32), and genotypic frequencies assuming either an additive or recessive model (OR=1.29, P=0.001 and OR=1.77, P =0.00018, respectively). When only lone AF cases were analyzed, the association remained significant (OR=1.50, P=0.001 for allelic association; OR=1.45, P=0.001 for an additive model; OR=2.24, P=0.000043 for a recessive model). Our results indicate that rs2106261 in ZFHX3 confers a significant risk of AF in a Chinese Han population. The study expands the association between ZFHX3 and AF to a non-European ancestry population and provides the first evidence of a cross-race susceptibility of the 16q22 AF locus.