国人载脂蛋白E基因多态性与冠心病发病之间的相关性

目的 探讨载脂蛋白E基因112bp与158bp位点多态性与血脂水平及冠心病发生之间的关系。方法采用生物化学法分别测量经冠状动脉造影证实的89例冠心病患者及43例正常人空腹血脂水平，应用聚合酶链反应限制片长多态性分析方法对载脂蛋白E基因DNA244bp的5’末端片段进行限制性片段长度多态性分析。结果冠心病组甘油三酯、总胆固醇、低密度脂蛋白、载脂蛋白B及脂蛋白（a）水平均高于对照组（P〈0．05），而载脂蛋白A1水平则低于对照组（P〈0、05）；冠心病组载脂蛋白Eε2基因型频率明显为低（P〈0．001）。结论载脂蛋白E基因多态性特征会明显影响人群中个体的血浆脂质水平，从而增加人群中个体发生冠心病的危险。     

Toll-Like Receptor (TLR)-9 rs352140 Polymorphism is an Immunopathology Protective Factor in Parkinson's Disease in the Northern Iranian Population

Background: Neuroinflammation and immunopathology in Parkinson's disease (PD) are believed to be associated with genetic and environmental factors. Objective: We conducted the current study to evaluate the Toll-like receptors (TLR4 and TLR9) genes polymorphism in patients with Parkinson's disease in northern Iran. Methods: We extracted DNA from peripheral blood samples of 100 sporadic cases of Parkinson's disease and 100 healthy-matched controls with the mean age of 69.98 and 71.94 years, respectively. Subsequently, single-nucleotide polymorphisms (SNPs) of TLR4 and TLR9 were genotyped using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Results were confirmed employing Sanger sequencing. For the analysis of our data, we used SNPStats and SPSS 22 software. Results: Our findings indicated that the allele distribution for rs352140 of TLR9 gene was significantly different in the PD group compared with the healthy controls (p=0.02). Moreover, rs352140 T allele was observed to be correlated with PD reduced risk (TT + TC vs. CC). The dominant rs352140 model was approved as the most acceptable inheritance model for fitting the data (OR 0.41, 95% CI 0.23-0.75, p=0.0031). Additionally, haplotype analysis revealed a significant correlation between TLR9 polymorphisms and Parkinson's disease. Conclusion: The results of this study indicated that rs352140T of TLR9 gene was a protective factor in Parkinson's disease. Furthermore, this SNP could be regarded as a prognostic factor. However, this conclusion should be confirmed by further investigations.     

The association between Cytotoxic T Lymphocyte Associated Antigen-4, Fas,Tumour Necrosis Factor-α gene polymorphisms and autoimmune hepatitis: A meta-analysis

BackgroundSeveral previous studies have assessed the association of Cytotoxic T Lymphocyte Associated Antigen-4, Fas, and Tumour Necrosis Factor-α gene polymorphisms with autoimmune hepatitis risk, but the results were inconsistent and inconclusive. We performed a meta-analysis to better evaluate these associations.MethodsPubMed, EMBASE and MEDLINE were searched in all languages. Overall odd ratios with 95% confidence intervals were calculated to assess the strength of associations using a fixed-effects or random-effects models.Results15 relevant studies were identified. No significant association was found between CTLA-4 + 49A/G and AH. TNF-α-308A/G was significantly associated with autoimmune hepatitis risk. Individuals with the “A” allele had a 67% increased risk of autoimmune hepatitis (odds ratio = 1.67, 95% confidence interval 1.11–2.52). The genotype “AA” was a potential predisposing factor for autoimmune hepatitis, when compared with the genotype “GG” and “AG + GG” (odds ratio = 2.71, 95% confidence interval 1.12–6.57; odds ratio = 2.14, 95% confidence interval 1.30–3.52). Besides, no significant association was found between the Fas-670G/A and TNF-α-238A/G polymorphisms and autoimmune hepatitis risk using any model.ConclusionThe meta-analysis identified the TNF-α-308 “A” allele as a predisposing factor for autoimmune hepatitis, whereas the genotype “GG” was a protective factor. This study did not find a significant association between CTLA-4 + 49A/G, Fas-670G/A, TNF-α-238A/G and susceptibility to autoimmune hepatitis.     

Protective role of DDAH2 (rs805304) gene polymorphism in patients with myocardial infarction

The purpose of the present study was to establish the role of DDAH gene polymorphisms in the risk of developing myocardial infarction (MI) in a clinical cohort of Mexican patients. One polymorphism (rs1498373) in the DDAH1 and three in the DDAH2 (rs805304, rs3131383, and rs805305) genes were performed by TaqMan genotyping assays in 473 patients with MI and 447 healthy unrelated controls. Similar distribution of DDAH1 and DDAH2 polymorphisms was observed in MI patients and healthy controls. Under a recessive model adjusted for age, gender, and obesity, the rs805304 C allele was associated with decreased risk of MI (OR = 0.70, 95% CI = 0.51–0.96, P = 0.030). The effect of the polymorphisms on various cardiovascular risk factors was analyzed. Under a recessive model adjusted for age and gender, the DDAH2 rs805304 C allele was associated with decreased risk of obesity (OR = 0.35, 95% CI = 0.22–0.57, P = 0.001). The three DDAH2 polymorphisms were in strong linkage disequilibrium. Our results suggest that the rs805304 C allele was associated with decreased risk of MI and decreased risk of obesity.     

Apolipoprotein C3 Gene Polymorphisms Are Not a Risk Factor for Developing Non-Alcoholic Fatty Liver Disease: A Meta-Analysis

Context:

Our objective was to evaluate the effect of gene polymorphisms of apolipoprotein C3 (APOC3) on the development of non-alcoholic fatty liver disease (NAFLD) in different populations.

Evidence Acquisition:

We performed a meta-analysis of all relevant studies published in the literature. A total of 115 clinical trials or reports were identified, but only seven trials met our inclusion criteria. A meta-analysis was performed according to the Cochrane Reviewers’ Handbook recommendations.

Results:

Five hospital-based and two population-based case-control studies were included in the final analysis. The overall frequency of APOC3 gene polymorphisms was 67.5% (1177/1745) in NAFLD and 68.8% (988/1437) in controls. The summary odds ratio for the association of gene polymorphisms of APOC3 and the risk of NAFLD was 1.03 (95% CI: 0.89-1.22),which was not statistically significant (P > 0.05).

Conclusions:

Our meta-analysis, while not ruling out possible publication bias, showed no association between gene polymorphisms of APOC3 and the risk of NAFLD development in different populations in the world.     

广西巴马长寿人群对氧磷酯酶-1基因多态性分析

目的探讨PON1基因Q192R位点在广西巴马地区不同人群中的频率及PON1基因多态性与巴马地区长寿现象的相关性。方法采用TaqMan探针实时荧光PCR技术对广西巴马长寿地区123例长寿老人(年龄90岁以上,长寿组)以及巴马长寿地区138例无长寿史的健康成年人(年龄24～87岁,对照1组)、巴马非长寿地区147例无长寿史的健康成年人(年龄48～89岁,对照2组)和南丹地区144例无长寿史的健康成年人(年龄21～83岁,对照3组)的PON1基因进行基因分型。结果长寿组与各对照组比较,等位基因和基因型分布差异存在统计学意义(P<0.05)。结论该多态性位点与地域有关,与巴马长寿地区的长寿现象是否有关还需进一步验证。     

Mitochondrial haplogroups and hypervariable region polymorphisms in schizophrenia: A case-control study

Previous studies have detected associations between mitochondrial haplogroups and schizophrenia (SZ). However, no study has examined the relationship between major mitochondrial DNA (mtDNA) haplogroups and SZ in the Chinese population. The aim of this study was to assess the association between mtDNA haplogroups and SZ genesis in the Chinese Han population. We used a case-control study and sequenced the mtDNA hypervariable regions (HVR1, HVR2, and HVR3) in the Han population. We analyzed mtDNA haplogroups and HVR polymorphisms in 298 SZ patients and 298 controls. The haplotypes were classified into 10 major haplogroups: A, B, CZ, D, F, G, M, N, N9a, and R. Statistical analysis revealed that only N9a showed a nominally significant association with protection from SZ [1.68% vs. 6.38%, p=0.004, OR=0.251 (0.092–0.680); after adjustment for age and sex: p=0.006, OR=0.246 (0.090–0.669)]. Three HVR polymorphisms were found to be nominally significantly different between subjects with SZ and controls, and all except one (m.204T>C) are linked to the N9a haplogroup. Our results indicate that mtDNA haplogroup N9a might be a protective factor for SZ.     

Study of Clinical and Genetic Risk Factors for Aspirin-induced Gastric Mucosal Injury

Background:

Current knowledge about clinical and genetic risk factors for aspirin-induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions.

Methods:

We recruited aspirin takers as the exposed group and healthy volunteers as the control group. The exposed group was categorized into two subgroups such as subgroup A as gastric mucosal injury diagnosed by gastroscopy, including erosion, ulcer or bleeding of the esophagus, stomach, or duodenum; subgroup B as no injury of the gastric mucosa was detected by gastroscopy. Clinical information was collected, and 53 single nucleotide polymorphisms were evaluated.

Results:

Among 385 participants, 234 were in the aspirin-exposed group. According to gastroscopy, 82 belonged to subgroup A, 91 belonged to subgroup B, and gastroscopic results of 61 participants were not available. Using the Chi-square test and logistic regression, we found that peptic ulcer history (odds ratio [OR] = 5.924, 95% confidence intervals [CI]: 2.115–16.592), dual anti-platelet medication (OR = 3.443, 95% CI: 1.154–10.271), current Helicobacter pylori infection (OR = 2.242, 95% CI: 1.032–4.870), male gender (OR = 2.211, 95% CI: 1.027–4.760), GG genotype of rs2243086 (OR = 4.516, 95% CI: 1.180–17.278), and AA genotype of rs1330344 (OR = 2.178, 95% CI: 1.016–4.669) were more frequent in subgroup A than subgroup B. In aspirin users who suffered from upper gastrointestinal bleeding, the frequency of the TT genotype of rs2238631 and TT genotype of rs2243100 was higher than in those without upper gastrointestinal bleeding.

Conclusions:

Peptic ulcer history, dual anti-platelet medication, H. pylori current infection, and male gender were possible clinical risk factors for aspirin-induced gastric mucosal injury. GG genotype of rs2243086 and AA genotype of rs1330344 were possible genetic risk factors. TT genotype of rs2238631 and TT genotype of rs2243100 may be risk factors for upper gastrointestinal bleeding in aspirin users.     

Cholesteryl ester transfer protein gene polymorphisms are associated with coronary artery disease in Corsican population (France)

The aim of the present study was to investigate the association between coronary artery disease (CAD) and Cholesterol Ester Transfer Protein (CETP) (gaaa)n polymorphisms of the CETP gene in Central Corsica island (France). The study group was composed by 300 unrelated Corsican patients with angiographically documented CAD and 300 unrelated healthy blood donors. Significant differences were observed in the distribution of CETP (gaaa)n alleles between the groups under study (p=0.03; chi(2): 16.8, df: 8). The occurrence of a long allele (408 bp) was higher in cases (12%) than in control group (2%), showing a 6.75-fold increased risk for CAD in Corsica patients (p=0.0055; OR=6.750; 95% CIs=1.47-31.00). The correlation of this polymorphism with the lipid profile (cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglycerides) in the patients group was determined. There was a significant association of the long alleles of CETP (gaaa)n with HDL-C levels. In the patient and in the control groups the LL genotypes had lower HDL-C compared with the SS and SL genotypes (p<0.0001). In summary our results suggest that the genetic variation at the CETP gene may play an important role in determining CAD in Corsican population.     

荧光杂交探针实时聚合酶链式反应快速检测甘露聚糖结合凝集素启动子区基因变异方法的建立

目的建立用荧光杂交探针实时聚合酶链式反应（Real-timePCR）检测人甘露聚糖结合凝集素（MBL）启动子区基因变异新型的基因分型法——Tm基因分型法。方法收集30例健康献血员外周抗凝全血,提取基因组DNA。通过LightCycler实时PCR仪描绘扩增的目标DNA片段的熔解曲线,根据熔解温度（Tm）峰值判定待测标本的基因变异类型。最后,用基因测序法检测PCR产物来验证Tm基因分型法的准确性。结果建立了新型的Tm基因分型法,且测定PCR产物的时间仅180min,检测结果与测序法完全吻合。结论Tm基因分型法检测人MBL启动子区基因变异快速、准确,重复性好,具有广泛的临床应用前景。