白细胞介素23 受体基因rs6682925 多态与冠心病发病的相关关系

目的:本研究探讨白细胞介素23受体(Interleukin 23 Receptor,IL23R)基因单核苷酸多态位点(rs1884444与rs6682925)与中国北方汉族人群冠心病发病的相关关系。方法:本研究采用病例-对照的设计方法,收集568名冠心病患者以及45岁以上、年龄及性别匹配的524名正常对照个体为研究对象,采用测序法检测IL23R rs1884444与rs6682925单核苷酸多态性基因型,分析IL23R基因rs1884444与rs6682925单核苷酸多态位点的基因型及等位基因的分布情况。结果:IL23R rs6682925与rs1884444单核苷酸多态位点的基因型频率符合Hardy-Weinberg定律。IL23R基因rs6682925单核苷酸多态位点的三种基因型分布频率(CC型,TC型和TT型)在冠心病组为22.9%,39.6%和37.5%,在对照组分别为41.7%,47.2%和11.1%,IL23R基因rs6682925单核苷酸多态位点C等位基因是冠心病发病的一个独立的危险因素(P0.05);IL23R基因rs1884444单核苷酸位点的基因型和等位基因的频率在对照组和冠心病组之间不存在统计学差异(P0.05)。Logistic回归校正性别、年龄、体重指数、吸烟、高血压、高脂血症、糖尿病等冠心病的易患因素后,IL23R基因rs6682925 C等位基因仍是冠心病发病一个独立危险因素。结论:在中国北方汉族人群中,IL23R基因rs6682925 C等位基因可能是冠心病发病的独立危险因素。     

apelin基因rs2235306位点多态性与哮喘的相关性研究

目的:探讨apelin基因rs2235306位点多态性与哮喘的相关性。方法:以外周血全血DNA为模板,应用四引物扩增受阻突变体系PCR(Tetra-primer ARMS PCR,T-ARMS-PCR)方法对158例哮喘患者(AS)和79例健康个体(NC)apelin基因rs2235306位点基因型进行分析,同时进行肺功能检查(FEV1、FVC、FEV1/FVC)。结果:AS组和NC组apelin基因rs2235306位点等位基因T和C频率分布具有统计学意义(X2=6.906,P=0.009,OR=1.688,95%CI=1.140-2.497),AS组C等位基因频率显著高于健康对照组;AS组和NC组基因型分布具有统计学意义(X2=14.243,P=0.000,OR=3.894,95%CI=1.861-8.149),其中CC基因型患哮喘的风险较高,为TT+TC基因型的3.894倍。AS轻度组和AS中重度组基因型CC和TT+TC频率及等位基因T和C频率比较均无统计学意义。结论:apelin基因rs2235306位点多态性和哮喘的发病具有一定的相关性,C等位基因可能是哮喘的遗传易感基因,CC基因型携带者哮喘的患病风险可能增加,但与哮喘的严重程度无明显相关性。     

易感基因多态性与支气管哮喘的相关性研究

目的:探讨白介素-4(Interleukin-4,IL-4)基因589位点、白介素-4受体(interleukin-4 receptor,IL-4R)基因576位点多态性与内蒙古地区汉族支气管哮喘患者是否存在遗传易感性,是否与血清总IgE浓度相关.方法:采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法检测内蒙古地区62例支气管哮喘患者和30例汉族正常人群IL-4基因的589位点、IL-4R基因的576位点多态性,进行基因型和基因频率分析,同时采用Elisa法检测患者血清总IgE浓度.结果:哮喘组IL-4基因启动子区-589(C/T)位点多态性分布频率与对照组比较,两组间基因型频率分析(X2=3.437,P=0.179),无显著性统计学差异(P＞0.05);两组基因频率分析(X2=9.405,P=0.002),有显著性差异(P＜0.05).哮喘组IL-4R基因启动子区-576(Q/R)位点多态性分布频率与对照组比较,两组间基因型频率分析(X2=0.815,P=0.665),无显著性统计学差异(P＞0.05),两组基因频率分析(X2=0.245,P=0.621),无显著性差异(P＞0.05).哮喘组血清总IgE浓度高于对照组,有显著性差异(t=6.367,P=0.00,P＜0.05).结论:内蒙古地区汉族人群哮喘组中,IL-4基因启动子区-589(C/T)位点多态性与支气管哮喘的发病无显著性差异;IL-4R基因-576(Q/R)位点多态性与支气管哮喘的发病无显著性差异;患者组血清总IgE显著高于对照组,但是与IL-4基因启动子区-589(C/T)位点多态性和IL-4R基因-576(Q/R)位点多态性没有相关性.     

CISH基因多态性与结核病易感性的相关性研究

目的:寻找肺结核的易感位点,探索宿主遗传因素差异对肺结核发病的影响,为肺结核的预防和药物研发提供理论依据。方法:对1218名汉族居民进行病例对照研究,其中病例组600例,对照组618例,进行流行病学调查和生化指标检查。运用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术检测CISH基因rs2239751和rs622502的基因型分布,探讨CISH基因多态性与中国汉族人群肺结核易感性的关联性。结果:CISH基因的rs2239751和rs622502等位基因分布均符合Hardy-Weinberg(H-W)遗传平衡定律(P0.05)。rs2239751位点基因型和等位基因分布在两组间差异有统计学意义,P值分别为0.013和0.01,并且携带C等位基因个体患肺结核的风险是携带A等位基因的个体1.16倍(95%CI=1.03-1.29,P=0.01)。rs2239751基因分型结果在女性病例组和对照组中差异有统计学意义,P值为0.007,OR(95%CI)为1.51(1.12-2.03)。rs2239751基因分型结果在45岁人群病例组和对照组中差异有统计学意义,P值为0.010,OR(95%CI)为1.32(1.07-1.64)。rs622502位点基因型和等位基因分布在两组间差异均无统计学意义(P0.05)。结论:在汉族人群中,rs2239751位点多态性可能是肺结核的危险因素之一,C等位基因为风险等位基因。rs2239751基因多态性与肺结核的关联性仅限于于女性和45岁人群。rs622502位点多态性可能与肺结核无关。     

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。     

胆囊收缩素及受体基因多态性与精神分裂症的相关性研究

目的：探讨胆囊收缩素（cholecystokinin,CCK）基因、胆囊收缩素A受体（cholecystokininAreceptor。CCKAR）基因和胆囊收缩素B受体（cholecystokinin A recepmr,CCKBR）基因多态性与精神分裂症之间的相关性。方法：采用聚合酶链式反应．限制性片段长度多态性方法,对420例精神分裂症患者（病例组）和455例健康个体（对照组）三个基因的6个单核苷酸多态性（single nucleotide polymorphism,SNPs）位点（rs11571842、rs13069836、rs1800908、rs1800857、rs1042047、rs4758092）的多态性进行检测。并比较两组人群中基因型和等位基因频率分布的差异。结果：对照组6个SNPs位点的基因型频率分布均符合Hardy-Weinbere平衡（P〉0．05）;CCKAR基因rs1800857位点基因型频率分布在精神分裂症组与正常对照组间存在显著性差异（P〈0．000）,病例组T等位基因频率显著高于对照组（P〈0．01）。结论：CCKAR基因多态性与精神分裂症相关,携带T等位基因的个体可能更容易患精神分裂症。     

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。     

雌激素受体α(ESR1)基因PvuⅡ和XbaⅠ位点基因多态性与HBV慢性感染的相关性研究

目的:探讨雌激素受体ESR1(Estrogen Receptor alpha gene)基因的PvuⅡ(rs2234693)和XbaⅠ (rs9340799)两个单核苷酸多态性(single nucleotide polymorphisms, SNPs)位点的基因多态性与乙型肝炎病毒HBV(Hepatitis B Virus)慢性感染的相关性,为控制HBV持续感染提供新的思路和科学依据。方法:选择107例慢性乙型病毒性肝炎患者为病例组及107例同期体检的健康人群为对照组,基于高分辨熔解曲线技术(High Resolution Melting,HRM)建立PCR-HRM分子诊断方法,检测其雌激素受体ESR1基因两个SNP位点rs2234693(TC)和rs9340799(AG)的基因多态性,并通过基因测序进一步验证,探讨上述两个SNP位点与HBV慢性感染的相关性。结果:病例组和健康对照组ESR1基因rs2234693(TC)位点的基因型频率比较差异具有统计学意义(P0.05),而两组间rs2234693位点等位基因频率比较差异没有统计学意义(P0.05);病例组和健康对照组间ESR1基因rs9340799(AG)位点的各基因型频率差异具有统计学意义(P0.05),慢性乙肝病例组GG基因型明显升高,两组间rs9340799位点等位基因频率差异亦具有统计学意义(P0.05)。Logistic回归分析显示rs9340799位点的G基因可增加HBV慢性感染的发病风险,A基因可降低HBV慢性感染的发病风险。结论:雌激素受体基因ESR1的rs9340799 (AG)位点的GG基因型和G等位基因可能是HBV感染慢性化的遗传易感基因,GG基因型与HBV的慢性感染具有一定的相关性。     

OPHN1基因rs492933位点多态性与秦巴山区汉族儿童非特异精神发育迟滞的相关性研究

OPHN1基因编码RhoGTP酶激活蛋白(RhoGAP), 是X连锁的与非特异性精神发育迟滞有关的基因之一。采用PCR-RFLP方法, 对234名陕西秦巴山区正常的汉族儿童以及精神发育迟滞(Mental retardation, MR)患者的OPHN1基因5′非翻译区中的单核苷酸多态位点(Single nucleotide polymorphism, SNP) rs492933的等位基因频率和基因型频率以及是否与非特异精神发育迟滞相关进行分析。结果发现: 这一位点基因频率C为0.826, T为0.174; MR组与对照组之间基因型频率和基因频率没有显著性差异, 边缘组与对照组之间基因型频率和基因频率也没有显著性差异。证明OPHN1基因内SNP rs492933的多态性与秦巴山区汉族儿童精神发育迟滞不存在相关性。     

IL-10基因启动子-627位点多态性与过敏性哮喘

目的：探讨白细胞介素-10（IL-10）启动子-627C／A基因多态性和等位基因频率与过敏性哮喘血清IgE、IL-10浓度以及病情严重程度的相互关系。方法：从哮喘病人DNA文库中选择青岛地区过敏性哮喘病人518例和健康志愿者501例,采用PCR—RFLP方法对IL．10基因启动子．627位点多态性进行观察,比较两组基因型和等位基因的分布频率,同时测定血清中总IgE、IL-10浓度和肺功能检查（FEV1、FVC、FEV1／FVC）。结果：轻度和中一重度哮喘组AA、CA和CC基因型所占比例分别为38．1％、46．0％、15．9％和45．6％、46．2％和8．2％（P=0．0168,X2=8．232,df=2）。A等位基因与哮喘病轻的严重程度有明显相关性（P〈0．05）。AA基因型哮喘病人血清的IgE浓度显著升高（P〈0．01）,但其血清IL-10浓度比CC基因型携带者明显降低（P〈0．01）。结论：IL-10基因启动子-627位点多态性与过敏性哮喘的发生有一定的相关性,等位基因A是哮喘患病的风险基因,而等位基因C则是哮喘病的保护基因。     

Association of two variants in the interleukin-6 receptor gene and premature coronary heart disease in a Chinese Han population

Two novel single nucleotide polymorphisms (SNPs; rs7529229 and rs2228145) in the interleukin-6 receptor (IL6R) gene have recently been associated with coronary heart disease (CHD) in a European population. We sought to replicate this finding and to investigate associations of these two SNPs with the severity and clinical phenotypes of premature CHD in a Chinese Han population. A total of 418 patients were studied, including 187 cases with coronary stenosis ≥50 % or acute myocardial infarction (males < 55 years and females < 65 years) and 231 controls without documented CHD. A ligase detection reaction was performed to detect rs7529229 and rs2228145. There were no differences between the controls and premature CHD groups in the frequencies for the three genotypes and alleles of rs7529229 and rs2228145 (all P > 0.05), nor did they differ between the two groups when grouped by gender (all P > 0.05). There were also no associations between these two SNPs and the severity of coronary lesions or clinical phenotypes of premature CHD (all P > 0.05). Our results do not support an association between rs7529229 or rs2228145 with premature CHD in the Chinese Han population. Further studies are warranted to elucidate the role of these two SNPs in the development of atherosclerosis and CHD.     

M31R and R335C polymorphic variants of the IL8RA gene in Russian and Buryat patients with atopic bronchial asthma

To test the M31R and R335C polymorphisms of the Il8RA gene for association with atopic bronchial asthma (BA), the allele and genotype frequency distributions of the polymorphisms were studied in Russian patients from Moscow and Buryat patients from Ulan-Ude. The study involved two Russian groups, one including 291 DNA samples of patients with atopic BA, and the other, 266 DNA samples of healthy people. The two Buryat groups included 124 and 152 DNA samples from patients with atopic BA and healthy people, respectively. The M31R polymorphism proved to be associated with atopic BA in Russians. Allele Arg and genotype Met/Arg suggested a higher risk of BA (OR= 4.45, P = 0.003 and OR = 4.58, P = 0.003, respectively), while allele Met and genotype Met/Metwere associated with a lower risk (OR = 0.22, P = 0.003 and OR = 0.22, P = 0.003, respectively). The R335C polymorphism was not associated with atopic BA in Russians and was in Buryats. Allele Arg and homozygous genotype Arg/Arg suggested a higher risk of the disease (OR = 3.06, P = 0.030 and OR = 3.20, P = 0.027, respectively), while allele Cys and genotype Arg/Cys suggested a lower risk (OR = 0.33, P = 0.030 and OR = 0.31, P = 0.027, respectively). The results support the role of the IL8RA gene in atopic BA.     

Association of IL1R polymorphism with HLA-B27 positive in Iranian patients with ankylosing spondylitis

Ankylosing spondylitis (AS) is one of the most common causes of inflammatory arthritis, with an estimated prevalence of 0.1-0.9%. Genetic factors have been strongly implicated in its aetiology, and heritability as assessed by twin studies has been estimated to be >90%. HLA- B27 is almost essential for inheritance of AS; it is not merely sufficient for explaining the pattern of familial recurrence of the disease. This study's purpose is to investigate the association of ankylosing spondylitis with single-nucleotide polymorphisms (SNPs) in the IL-1 family: IL-1a (-889C/T) rs1800587, IL-1b (-511C/T) rs16944, IL-1b (+3962C/T) rs1143634, IL-1R (Pst-1 1970C/T) rs2234650 and IL-1RA (Mspa-1 11100C/T) rs315952. 99 unrelated Iranian AS patients and 217 healthy control subjects were selected. Cytokine typing was performed by the polymerase chain reaction with sequence-specific primers assay. The allele and genotype frequencies of the polymorphisms were determined: The IL1α rs1800587, IL1β rs16944 and IL1β rs1143634 were not significantly associated with AS. Genotype frequencies at IL1R rs2234650 differed between cases and controls (χ(2)=8.85; p=0.01); the IL1R rs2234650 C/T and T/T genotypes were less common in AS patients than controls. The IL1R rs2234650 C/T genotype was inversely associated with AS comparing with the IL1R rs2234650 C/C genotype (OR=0.48; p=0.005). IL1R rs2234650 C/T genotype was less common in patients than controls (OR=0.37; p=0.02).Furthermore IL1R rs2234650 T allele was strongly associated with HLA-B2702 patients rather than HLA-B2705 but was not associated with HLA-B27 negative patients (OR=0.33; p=0.01). Polymorphisms of IL1α rs1800587, IL1β rs16944 and IL1β rs1143634 were not significantly associated with ankylosing spondylitis but inversely in this study IL1R rs2234650 was significantly associated and carriage of T allele in IL1R rs2234650 seems to be protective, while carriage of C allele result in two fold higher risk of developing AS.     

Potential association of obesity with IL6 G-174C polymorphism and TTV infections

Polymorphisms in IL6, ACE and ATR genes are associated with obesity. Torque Teno virus (TTV) seems to be able to interfere with production of some proinflammatory cytokines associated with obesity and related phenotypes. The aim of this study was to test the potential association between obesity, TTV infection and the IL6 G-174C (rs1800795), ACE I/D (rs4646994), AT1R A1166C (rs5186) polymorphisms. The polymorphisms and the presence of TTV were detected in blood samples from 150 obese and 150 normal-weight, healthy subjects using PCR based methods. IL6-174 CC genotype was more frequent in all obese patients (P=0.02) and in patients without TTV infections (P=0.03) than in controls. Obese women had more frequent TTV infections compared with normal-weight women (P=0.046). Obese subjects, regardless of gender (women P=0.03, men P=0.04), and healthy normal-weight men (P<0.01) carriers of AT1R C allele had higher triglycerides levels compared with non-carriers. The frequency of TTV in the control group (70.67%) was similar to data reported in other populations. The present study indicated that IL6-174 CC genotype and TTV infections in women could be associated with the common form of obesity.     

An association study between IL1RAPL2 gene and non-specific mental retardation in Chinese children

Non-specific mental retardation (NSMR) is one of common children psychiatric diseases with a high prevalence (1–3%). Here we investigated the association between the genetic variants of IL1RAPL2 gene and NSMR in the children of QinBa region of China. We chose five common SNPs of IL1RAPL2, examined their individual genotype frequencies using the conventional polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) method, and evaluated the association between these genetic polymorphisms and NSMR with the suitable biostatistic software. The allele and genotype distributions of two SNPs (rs5962298 and rs9887672) showed significant differences between the control and NSMR groups (allele: p = 0.020 and 0.017; genotype: p = 0.025 for rs9887672 respectively). The distribution differences became more significant in girls, but disappeared in boys, suggesting a gender effect. Taken together, we provide substantial evidence that IL1RAPL2 conferred a NSMR susceptibility to children of Qinba region in China. In future, further work should be carried out to scan mutations and to investigate the specific-gender effect in this gene.     

Polymorphism of interleukins and interleukin receptor genes: population distribution and association with atopic bronchial asthma

Population distribution and pathogenetic significance for bronchial asthma (BA) of the eight polymorphic variants of six interleukin--(IL) and interleukin receptor genes, C-589T, G/C 3'-UTR IL4, C-703T IL5, T113M IL9, Q551R, 150V IL4RA, and G1972A IL5RB, was examined. In the population samples of Russians, Tajiks, Buryats, and Tuvinians racial and ethnic specificity of these polymorphisms was established. These specific features were manifested as population-specific "enetic portraits" in respect of polymorphic allele frequencies. Analysis of the BA patients and their relatives from Tomsk by use of transmission/disequilibrium test (TDT) revealed the presence of a statistically significant association between the C-703 IL5 allele and the disease (P = 0.005). This is the first evidence of an association between the IL5 gene polymorphism and BA.     

An ADAM33 Polymorphism Associates with Progression of Preschool Wheeze into Childhood Asthma: A Prospective Case-Control Study with Replication in a Birth Cohort Study

Background

The influence of asthma candidate genes on the development from wheeze to asthma in young children still needs to be defined.

Objective

To link genetic variants in asthma candidate genes to progression of wheeze to persistent wheeze into childhood asthma.

Materials and Methods

In a prospective study, children with recurrent wheeze from the ADEM (Asthma DEtection and Monitoring) study were followed until the age of six. At that age a classification (transient wheeze or asthma) was based on symptoms, lung function and medication use. In 198 children the relationship between this classification and 30 polymorphisms in 16 asthma candidate genes was assessed by logistic regression. In case of an association based on a p<0.10, replication analysis was performed in an independent birth cohort study (KOALA study, n = 248 included for the present analysis).

Results

In the ADEM study, the minor alleles of ADAM33 rs511898 and rs528557 and the ORMDL3/GSDMB rs7216389 polymorphisms were negatively associated, whereas the minor alleles of IL4 rs2243250 and rs2070874 polymorphisms were positively associated with childhood asthma. When replicated in the KOALA study, ADAM33 rs528557 showed a negative association of the CG/GG-genotype with progression of recurrent wheeze into childhood asthma (0.50 (0.26-0.97) p = 0.04) and no association with preschool wheeze.

Conclusion

Polymorphisms in ADAM33, ORMDL3/GSDMB and IL4 were associated with childhood asthma in a group of children with recurrent wheeze. The replication of the negative association of the CG/GG-genotype of rs528557 ADAM33 with childhood asthma in an independent birth cohort study confirms that a compromised ADAM33 gene may be implicated in the progression of wheeze into childhood asthma.     

An Interleukin 13 Polymorphism Is Associated with Symptom Severity in Adult Subjects with Ever Asthma

Different genes are associated with categorical classifications of asthma severity. However, continuous outcomes should be used to catch the heterogeneity of asthma phenotypes and to increase the power in association studies. Accordingly, the aim of this study was to evaluate the association between single nucleotide polymorphisms (SNPs) in candidate gene regions and continuous measures of asthma severity, in adult patients from the general population. In the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (www.geird.org), 326 subjects (aged 20–64) with ever asthma were identified from the general population in Verona (Italy) between 2007 and 2010. A panel of 236 SNPs tagging 51 candidate gene regions (including one or more genes) was analysed. A symptom and treatment score (STS) and pre-bronchodilator FEV₁% predicted were used as continuous measures of asthma severity. The association of each SNP with STS and FEV₁% predicted was tested by fitting quasi-gamma and linear regression models, respectively, with gender, body mass index and smoking habits as potential confounders. The Simes multiple-test procedure was used for controlling the false discovery rate (FDR). SNP rs848 in the IL13 gene region (IL5/RAD50/IL13/IL4) was associated with STS (TG/GG vs TT genotype: uncorrected p-value = 0.00006, FDR-corrected p-value = 0.04), whereas rs20541 in the same gene region, in linkage disequilibrium with rs848 (r² = 0.94) in our sample, did not reach the statistical significance after adjusting for multiple testing (TC/CC vs TT: uncorrected p-value = 0.0003, FDR-corrected p-value = 0.09). Polymorphisms in other gene regions showed a non-significant moderate association with STS (IL12B, TNS1) or lung function (SERPINE2, GATA3, IL5, NPNT, FAM13A) only. After adjusting for multiple testing and potential confounders, SNP rs848 in the IL13 gene region is significantly associated with a continuous measure of symptom severity in adult subjects with ever asthma.