Impact of the PDE4D gene polymorphism and additional SNP–SNP and gene–smoking interaction on ischemic stroke risk in Chinese Han population

Aims: To investigate the association between phosphodiesterase 4D gene (PDE4D) gene single nucleotide polymorphisms (SNPs) and ischemic stroke (IS) risk, and impact of additional SNP- SNP and gene- smoking interaction on IS risk in Chinese population.

Methods: A total of 1228 subjects (666 males, 562 females) were selected, including 610 IS patients and 618 control subjects. Logistic regression model was used to examine the association between SNPs in PDE4D gene and IS risk. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the SNP- SNP and gene- smoking interaction.

Results: IS risks were significantly higher in carriers of A allele of rs12188950 polymorphism than those with GG genotype (GA + AA vs. GG), adjusted OR (95%CI) = 1.61 (1.26–2.19), and also significantly higher in carriers of T allele of rs966221 polymorphism than those with CC (CT + TT vs. CC), adjusted OR (95%CI) = 1.82 (1.39–2.23). We found that there was a significant SNP- SNP interaction between rs966221 and rs12188950. Subjects with CT or TT of rs966221 and GA or AA of rs12188950 genotype have the highest IS risk, compared to subjects with CC of rs966221 and GG of rs12188950 genotype, OR (95%CI) was 3.52 (2.68–4.69). We also found a significant gene–environment interaction between rs966221 and smoking. Smokers with CT or TT of rs966221 genotype have the highest IS risk, compared to never smokers with CC of rs966221 genotype, OR (95%CI) was 3.97 (2.25–5.71).

Conclusions: Our results support an important association of rs966221 and rs12188950 minor allele and its interaction with increased risk of IS risk, and additional interaction between rs966221 and smoking.     

CCR5基因多态性与乙型肝炎病毒感染相关性的研究进展

趋化性细胞因子和趋化性细胞因子受体在抗病毒免疫中发挥了重要作用。乙型病毒性肝炎是由其表达的抗原系统及其抗体所介导的特异性免疫反应和非特异性的以细胞因子为主的炎症介质导致的肝细胞损伤。CCR5作为趋化性细胞因子受体在乙型病毒性肝炎的发生发展中起重要作用。本文主要讲述CCR5基因的结构和功能,及在编码区和启动子区的多态性与HBV感染的相关性研究。     

Loss of human β-defensin 1, 2, and 3 expression in oral squamous cell carcinoma

Introduction:  Human β-defensins (HBDs) are cationic, antimicrobial peptides produced by epithelial cells and involved in various aspects of the innate and acquired immune responses. They are expressed by oral tissues as constitutive and inducible genes. Recently, single nucleotide polymorphisms (SNPs) of β-defensins have been correlated with increased susceptibility to certain diseases. Studies have reported altered expression of β-defensins in cancers suggesting their involvement in carcinogenesis. The purpose of this study was to evaluate the regulation of HBD-1 (also published as DEFB1), HBD-2 (DEFB4) and HBD-3 (DEFB103A) ( http://www.genenames.org/index.html ) and HBD-1 SNPs in oral squamous cell carcinoma cell lines (OSCC) and healthy gingival keratinocytes.
Methods:  β-defensin expression was quantitatively assessed using real-time polymerase chain reactions in OSCC and control cell lines after exposure to interleukin-1β, tumor necrosis factor-α, and interferon-γ. Control data were obtained in a previous study. DNA from 19 OSCC cell lines and 44 control subjects were extracted and the HBD-1 region spanning the 5' untranslated region to the first intron was sequenced and analysed for SNP identification and distribution.
Results:  HBD-1 and HBD-2 basal messenger RNA expression were significantly lower in OSCC. In addition, the ability to be induced was significantly reduced in OSCC for all three β-defensins. Four HBD-1 SNPs were differentially distributed between cancer and control populations. Genotype distribution at the HBD-1 locus also suggested loss of heterozygosity in OSCC.
Conclusions:  The genetic variation observed in OSCC compared with that in control cell lines may account for differences in β-defensin expression. These results suggest a putative role for β-defensins in carcinogenesis and indicate that β-defensins may be useful markers of OSCC.     

Comprehensive association analysis of APOE regulatory region polymorphisms in Alzheimer disease

Several recent case-control studies have examined the association between single nucleotide polymorphisms (SNPs) in the promoter region of the apolipoprotein E gene (APOE) and risk of Alzheimer disease (AD), with conflicting results. We assessed the relation between five APOE region SNPs and risk of AD in both case-control and family-based analyses. We observed a statistically significant association with the +5361T allele in the overall case-control analysis (P value=0.04) after adjusting for the known effect of the APOE-4 allele. Further analysis revealed this association to be limited to carriers of the APOE-4 allele. Age-stratified analyses in the patients with age at onset of 80 years or greater and age-matched controls showed that the –219T allele (P value=0.009) and the +113C allele (P value=0.03) are associated with increased risk of AD. Despite these findings, haplotype and family-based association analyses were unable to provide evidence that the APOE region SNPs influenced risk of AD independent of the APOE-4 allele. In addition to risk, we tested for association between the SNPs and age at onset of AD, but found no association in the case-control or family based analyses. In conclusion, SNPs +5361, or a SNP in strong linkage disequilibrium, may confer some additional risk for developing AD beyond the risk due to APOE-4; however, the effect independent of APOE-4 is likely to be small.     

Analysis of the association of IL1B (C+3954T) and IL1RN (intron 2) polymorphisms with dental implant loss in a Brazilian population

Background: Although dental implants have a high success rate, failures occur, in spite of adequate clinical conditions. Together with the observation that multiple implant losses occur in certain groups of individuals (clusterization phenomenon), this suggests that host response may influence implant failure. Little is known about the influence of genetic susceptibility on implant loss. Interleukin (IL)-1β and IL-1ra are believed to play a key role in the immune-inflammatory response, and polymorphisms IL1B (C+3954T) and IL1RN (intron 2) are shown to alter the coding proteins expression.
Objectives: The aim of this study was to investigate the association between dental implant loss and polymorphisms IL1B (+3954) and IL1RN (intron 2).
Material and methods: The study population ( n =266) was divided into Test group (T) – 90 subjects with implant loss, and Control group (C) – 176 subjects without any implant failure. Genotyping was performed by PCR-RFLP.
Results: The number of present teeth was observed to influence implant loss. No differences in genotype and allele frequencies between C and T were found for IL1B (+3954) and IL1RN (intron 2) polymorphisms. However, the analysis of the whole study population (control and test groups) showed that genotype 2/2 was significantly more frequent in individuals with multiple implant losses ( n =35) than in individuals that lost up to a single implant ( n =231) (OR: 3.07, IC: 1.13–8.34, P =0.027).
Conclusion: It was observed that number of teeth and edentulism were associated with implant loss. Genotype 2/2 of IL1RN polymorphism was significantly more frequent in patients who presented multiple losses, which suggests that the clusterization phenomenon has a genetic basis.     

肿瘤坏死因子基因型多态性与肾移植受者急性排斥反应的关系

目的：探讨肾移植受者外周血中肿瘤坏死因子（TNF-α）基因多态性与急性排斥反应的关系。方法：应用序列特异性引物聚合酶链反应（PCR—SSP）测定62例肾移植受者外周血中TNF-α的基因型,并结合供受者HLA配型情况,比较各基因型对急性排斥反应发生率的影响。结果：在HLA—DR错配的情况下,TNF—α等位基因为高分泌型者,其术后急性排斥反应发生率较低分泌型者高（P〈0．05）。结论：TNF-α基因型对肾移植排斥反应发生率有明显影响,可据此或可制定更为合理的个体化免疫抑制治疗方案。     

载脂蛋白A1、B基因多态性对非创伤性股骨头坏死发生的影响

目的:探讨载脂蛋白A1、B基因多态性对非刨伤性股骨头坏死(avascular necrosis of the femoral head,ANFH)发生的影响.方法:应用聚合酶链反应对中国北方汉族143例ANFH患者和92例正常人分别扩增含Apo AI基因启动子-75 bp和第一内舍子 83 bp及Apo B基因Eco RI、XbaI和3-VNTR的DNA片段,限制性内切酶酶切扩增产物,琼脂糖凝胶电泳分离基因多态性.结果:Apo A1基因启动子-75 bp处,ANFH患者中A/A基因型频率明显高于正常组(P＜0.01),而G/A基因型频率明显低于正常组(P＜0.01).Apo AI内舍子 83 bp位点,Apo B基因Eco RI、Xba I位点和3-VNTR区域ANFH患者组和正常组基因型及等位基因频率分布无统计学差异.结论:Apo A1基因启动子区域-75bp位点A/A型可能是非创伤性股骨头坏死易感基因之一,但未能发现Apo A1第一内舍子 83 bp位点及Apo B基因Eco RI、XbaI和3-VNTR位点多态性与非创伤性股骨头坏死发生有明显的关系.     

Association of APOE e4 and cerebrovascular pathology in traumatic brain injury

BACKGROUND: Previous studies have found the e4 allele of the apolipoprotein E gene (APOE e4) is associated with an unfavourable outcome after head injury, but this has not been related to specific pathological features. OBJECTIVES: This study tested the postulate that head injured patients with APOE e4, amounting to approximately a third of the population, are selectively predisposed to one or more of the different pathological features that constitute the response to traumatic brain injury (TBI), and that this underlies the association of APOE e4 with poor clinical outcome. METHODS: Included in the study were 239 fatal cases of TBI (1987-1999) for which APOE genotypes were determined from archival tissue. For each case, specific pathological features of trauma were recorded by researchers blinded to the APOE e4 status. Of the 239 cases examined, 83 (35%) were APOE e4 carriers and 156 (65%) were non-carriers. RESULTS: Possession of APOE e4 was associated with a greater incidence of moderate or severe contusions (42% v 30% for carriers versus e4 non-carriers; p = 0.05) and there was a trend towards a greater incidence of severe ischaemic brain damage (54% v 42%; p = 0.08). Significant differences were not noted between the other pathological features examined. CONCLUSIONS: Possession of APOE e4 is associated with a greater incidence of moderate/severe contusional injury and severe ischaemic brain damage in fatal cases of TBI. This may be relevant to the relatively poor outcome from traumatic brain injury in patients with APOE e4 identified in clinical studies.     

GRIA1、GRM3、TCF4基因单核苷酸多态性与精神分裂症的关联研究

目的 探讨GRIA1、GRM3和TCF4基因单核苷酸多态性与精神分裂症的关联,为精神分裂症的遗传学研究提供参考。 方法 选取昆明医科大学第一附属医院精神科的663例符合《精神障碍诊断与统计手册（第4版）》（DSM-IV）诊断标准的精神分裂症患者为病例组,以昆明市第一人民医院体检中心的690例健康人为对照组,使用SNaPshot基因分型方法对受试者GRIA1、GRM3、TCF4三个候选基因12个SNPs进行基因分型,并进行遗传学分析。 结果 GRM3多态性位点rs6465084的A等位基因频率与对照组相比差异有统计学意义（P=0.027）;以性别特异性做相关分析,表明多态性位点rs6465084 A等位基因频率在男性精神分裂症患者与正常对照组中差异有统计学意义（P=0.02）。 结论 GRM3多态性位点rs6465084可能与精神分裂症存在关联,其等位基因A可能增加精神分裂症的发病风险。