Association of the Single-Nucleotide Polymorphism and Haplotype of the Complement Receptor 1 Gene with Malaria

PurposeAlthough the polymorphisms of erythrocyte complement receptor type 1 (CR1) in patients with malaria have been extensively studied, a question of whether the polymorphisms of CR1 are associated with severe malaria remains controversial. Furthermore, no study has examined the association of CR1 polymorphisms with malaria in Chinese population. Therefore, we investigated the relationship of CR1 gene polymorphism and malaria in Chinese population.ResultsThere were no significant differences in the genotype, allele and haplotype frequencies of CR1 gene rs2274567 G/A, rs4844600 G/A, and rs2296160 C/T polymorphisms between patients with malaria and controls. Furthermore, there was no association of polymorphisms in the CR1 gene with the severity of malaria in Chinese population.ConclusionThese findings suggest that CR1 gene rs2274567 G/A, rs4844600 G/A, and rs2296160 C/T polymorphisms may not be involved in susceptibility to malaria in Chinese population.     

血管紧张素原、血管紧张素Ⅱ一型受体基因多态性与原发性高血压的相关性研究

目的 :探讨血管紧张素原AGT(M2 3 5T)、血管紧张素Ⅱ一型受体AT1 R(A1166C)基因多态性与中国四川籍人群原发性高血压(EH)的关系。方法 :采用聚合酶链反应 (PCR)及限制性片段长度多态性分析 (RFLP)方法分析人类白细胞染色体DNA中AGT、AT1 R基因多态性。结果 :12 2例EH病例组与 87例正常对照组AGT等位基因频率T、M分别为 :T :0 .82 8vs 0 .661,M :0 .172vs 0 .3 3 9。AT1 R等位基因频率A、C分别为 :A :0 .968vs 0 .989,C :0 .0 3 2vs 0 .0 11。各基因型频率及等位基因频率符合Hardy Weinberg平衡定律。EH病例组AGT基因T等位基因频率和TT型明显高于对照组(χ2 =11.7,P <0 .0 1和 χ2 =15 .6,P <0 .0 1)。结论 :AGT基因多态性与EH密切相关 ;而AT1 R基因多态性与EH无关。     

Scavenger Receptor Class B Type 1 Gene rs5888 Single Nucleotide Polymorphism and the Risk of Coronary Artery Disease and Ischemic Stroke: A Case-Control Study

Background: Our previous studies have showed that the rs5888 single nucleotide polymorphism (SNP) in Scavenger receptor class B type 1 (SCARB1) gene is associated with serum lipid levels in the general Chinese populations. The present study was undertaken to detect the associations between rs5888 SNP and the risk of coronary artery disease (CAD) and ischemic stroke (IS).Methods: A total of 1,716 unrelated subjects (CAD, 601; IS, 533; and healthy controls, 582) were included in this study. Genotyping of the rs5888 SNP were determined by polymerase chain reaction and restriction fragment length polymorphism.Results: The genotypic frequencies of SCARB1 rs5888 SNP were different between CAD patients and controls, the subjects with TT genotype had high risk of CAD (OR = 1.76, P = 0.038 for TT vs. CC; and OR = 1.75, P = 0.036 for TT vs. CC/CT). There was no significant association between genotypes and the risk of IS. Further analysis showed that the subjects with TT genotype in the total population had lower levels of high-density lipoprotein cholesterol than the subjects with CC/CT genotypes (P < 0.05), the subjects with TT genotype in controls but not in CAD or IS patients had higher levels of serum LDL-C and ApoB than those with CC genotype (P < 0.05 for each).Conclusions: The present study suggests that the SCARB1 rs5888 SNP influences serum lipid levels, and is associated with the risk of CAD.     

H型高血压患者血管紧张素转化酶基因多态性对其活性及血脂水平影响的探究

目的 探究H型高血压患者和普通高血压患者中不同基因型的血管紧张素转化酶的活性差异以及其对血脂水平的影响.方法 实验采用了聚合酶链式反应的方法,分别鉴定68例H型高血压患者和64例普通型高血压患者血管紧张素转化酶的基因型,并且对不同基因型的血管紧张素转化酶的活性和对应的血脂水平进行了检测.结果 利用SPSS19.0对数据进行分析,H型高血压和普通高血压患者的不同基因型的血管紧张素转化酶活性的差异均具有统计学意义(P＜0.01),但血管紧张素水平的差异无统计学意义.血管紧张素转化酶基因多态性对血脂水平影响的研究表明,H型高血压组中缺失型纯合子(DD型)与插入型杂合子(ID型)和插入型纯合子(Ⅱ型)相比较,DD型血脂水平明显偏高,其中胆固醇(TC)(P＜0.01),高密度脂蛋白(HDLD),低密度脂蛋白(LDLC)和载脂B的水平的差异均具有统计学意义(P＜0.05).普通高血压组仅HDLC,LDLC和载脂B的差异具有统计学意义(P＜0.05).结论 在H型高血压和普通型高血压患者中,血管紧张素转化酶的基因多态性与血管紧张素转化酶的活性及血脂含量有关.H型高血压患者的DD型的血管紧张素转化酶的活性最高,并且血脂水平偏高,其中胆固醇含量增高最为明显,更加容易患高血脂症.     

β2肾上腺素能受体基因+491C/T多态性与新疆哈萨克族人血脂的关系

目的:研究β2肾上腺素能受体（β2-AR）基因+491C/T多态性在新疆哈萨克族人群中的分布及其与甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白（HDL－C）、低密度脂蛋白（LDL-C）的关系。方法: 采用横断面调查方法采集528例30 -60岁哈萨克族人的遗传标本，采用酚/氯仿法提取外周血白细胞基因组DNA，应用PCR－RFLP技术，检测β2-AR基因+491C/T基因型，分析基因型及等位基因在该人群中的分布频率及其与TG、TC、HDL-C、LDL-C水平的关系。结果:该人群β2-AR基因+491C/T位点检测出两种基因型CC、CT,分布频率分别为98.86%、1.14%，等位基因C、T频率为99.43％、0.57％，符合Hardy-Weinberg平衡(χ2=0.017, P=0.896)。两种基因型间TC、LDL-C水平有增高趋势，但差异无统计学意义；在女性中CT基因型携带者血清LDL-C水平明显高于CC基因型，差异有统计学意义（P＝0.038）；按WH01997血脂防治建议标准分类后，CT基因型、T等位基因频率与高LDL－C相关（P＝0.031）。结论:新疆哈萨克人群存在β2-AR 基因+491C/T多态性，该人群尤其是女性中CT型携带者血清LDL-C水平明显增高，CT基因型、T等位基因频率与高LDL-C水平相关，提示该多态性可能是哈萨克人群尤其是女性的高LDL-C的易感因素。     

XbaI GLUT1 Gene Polymorphism and the Risk of Type 2 Diabetes with Nephropathy

Altered expression of the facilitated glucose transporter GLUT1 affects pathways implicated in the pathogenesis of diabetic nephropathy. There is indication that variation of GLUT1 gene (SLC2A1) contributes to development of microangiopathy in diabetes mellitus type 2 (DM) patients. A genetic association study involving Caucasians was carried out to investigate the role of XbαI polymorphism in the GLUT1 gene in diabetic nephropathy (DN). Study population (n = 240) consisted of 148 unrelated patients with DM (92 cases with diabetic nephropathy (DN)), and of 92 matched healthy control subjects. Diabetic nephropathy was defined as persistent albuminuria (> 300 mg/24 h) and/or renal failure, in the absence of non-diabetes induced renal disease. The analysis showed that the risk of developing DM and DN in XbaI(−) carriers, when healthy individuals were considered as controls, was two-fold: odds ratio (OR) 2.08 [95% confidence interval (1.14–3.79)]. However, there was no evidence of association between XbaI(−) and DN when patients with DM and without DN were considered as controls: OR = 1.12 (0.55–2.26). Thus, the GLUT1 XbaI(−) allele is associated with DM, and possibly with a more severe form of the disease that can lead to development of DN.     

Association between the Interleukin‐6 Gene −572 C/G Polymorphism and the Risk of Type 2 Diabetes Mellitus: A Meta‐Analysis of 11,681 Subjects

The association between the interleukin‐6 (IL‐6) gene ?572 C/G (rs1800796) polymorphism and type 2 diabetes mellitus (T2DM) risk remains controversial. Thus, we performed this meta‐analysis by searching PubMed, Embase, Web of Science, CBMdisc and CNKI databases until January 30, 2012. In addition, hand searching of the references of identified articles was performed. A total of 10 case–control studies including 11,681 subjects were selected to evaluate the possible association. Our results showed evidence for significant association between the IL‐6 gene ?572 C/G polymorphism and T2DM risk (for G allele vs. C allele: odds ratio [OR] = 1.29, 95% confidence interval [CI] = 1.09–1.52, P = 0.002, P = 0.008 after Bonferroni testing; for G/G vs. C/C: OR = 1.89, 95% CI = 1.51–2.37, P < 0.00001, P < 0.00004 after Bonferroni testing; for GG vs. G/C + C/C: OR = 1.75, 95% CI = 1.20–2.56, P = 0.004, P = 0.016 after Bonferroni testing; for G/G + G/C vs. C/C: OR = 1.32, 95% CI = 1.11–1.57, P = 0.001, P = 0.004 after Bonferroni testing). In addition, similar results were obtained in the subgroup analysis based on ethnicity. In summary, the present meta‐analysis suggests a significant association between the IL‐6 gene ?572 G allele and increased risk of T2DM.     

PTPN22 Gene Polymorphism (C1858T) Is Associated with Susceptibility to Type 1 Diabetes: A Meta‐Analysis of 19,495 Cases and 25,341 Controls

The protein tyrosine phosphatase N22 (PTPN22) gene C1858T polymorphism has been reported to be associated with susceptibility to type 1 diabetes (T1D) in relatively small sample sizes. This study aimed at investigating the pooled association by carrying out a meta‐analysis on the published studies. The Medline, EBSCO, and BIOSIS databases were searched to identify eligible studies published in English before June 2012. The association was assessed by odds ratio (OR) with 95% confidence intervals (CI). The presence of heterogeneity and publication bias was explored by using meta‐regression analysis and Begg's test, respectively. A total of 28 studies were involved in this meta‐analysis. Across all populations, significant associations were found between the PTPN22 C1858T polymorphism and susceptibility to T1D under genotypic (TT vs. CC [OR = 3.656, 95% CI: 3.139–4.257], CT vs. CC [OR = 1.968, 95% CI: 1.683–2.300]), recessive (OR = 3.147, 95% CI: 2.704–3.663), and dominant models (OR = 1.957, 95% CI: 1.817–2.108). In ethnicity‐ and sex‐stratified analyses, similar associations were found among Caucasians and within Caucasian male and female strata. The meta‐analysis results suggest that the PTPN22 C1858T polymorphism was associated with susceptibility to T1D among the Caucasian population, and males who carried the ‐1858T allele were more susceptible to T1D than females.     

健康人补体受体1基因单核苷酸多态性位点与其红细胞表面分子水平的相关性

目的 探讨健康人补体受体1(complement receptor type 1,CR1)基因单核苷酸多态性(single nucleotide polymorphisms,SNP)位点与红细胞表面CR1分子水平的相关性.方法 采用多重PCR-荧光标记单碱基延伸-标签微阵列杂交基因分型技术,检测215例受试者CR1基因5个标签SNP,并采用流式细胞术测定其中81例样本红细胞CR1分子水平.采用Arlequin3.11软件对各SNP位点基因型频率进行哈温平衡(Hardy-Weinberg equilibrium,HWE)检验,采用SPSS 13.0软件对健康人CR1基因SNP位点基因型及等位基因分布的性别差异、不同基因型人群红细胞CR1分子水平差异和影响红细胞CR1分子水平的单因素和多因素进行统计学分析.结果 健康人CR1基因SNP位点基因型及等位基因分布性别间的差异无统计学意义(P＞0.05);健康人红细胞CR1几何平均荧光强度比值(the geometric mean fluorescence intensity ratio of CR1,CR1-GMFIR)为3.36±1.26.rs11118167T＞C和rs9429945C＞T位点各基因型组对应的红细胞CR1分子水平总体比较,差异具有统计学意义(分别为P＜0.01和P＜0.05),两两比较时,rs11118167T＞C位点TC、CC基因型携带者低于TT基因型者,rs9429945C＞T位点CT、TT基因型携带者低于CC基因型者(P值均＜0.01).在年龄、性别、5个标签SNP位点各基因型中,CR1-GMFIR与rs4844600G＞ A(GG/GA/AA)、rs9429945C＞ T(CC/CT/TT)、rs1 1118167T＞C(TT/TC/CC)均呈负相关(分别为P＜0.05,P＜0.01,P＜0.01),影响CR1-GMFIR的最主要因素为rs11118167T＞ C(P ＜0.01),其次为rs9429945C＞ T(P＜0.01).结论 rs11118167T＞C和rs9429945C＞T是红细胞CR1分子水平的主要影响因素.     

The Influence of C3435T Polymorphism of the ABCB1 Gene on Genetic Susceptibility to Depression and Treatment Response in Polish Population - Preliminary Report

Background: Despite the high prevalence of depression, the mechanism of the origin of this disease as well as the causes of resistance to therapy in some patients are still not fully understood. Increasingly, the possible role of genetic factors is considered. One of them is polymorphisms in the ABCB1 (MDR1) gene which encodes P-glycoprotein, responsible for the transport of xenobiotics, including antidepressant drugs, through the blood-brain barrier.Methods: C3435T was evaluated in 90 patients with recurrent depressive disorders (rDD). Genotyping was performed using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).Results: The obtained results indicate that the TT genotype occurred more frequently among patients with rDD than in healthy volunteers (p=0.0441). Also, at least one C allele was present significantly less frequent in the study group than in healthy individuals (p=0.0300). The severity of depressive symptoms was higher among patient with the CC genotype in comparison with the other genotypes (p=0.0106) but treatment response to antidepressants was better in this group than among patients with CT or TT genotypes (p=0.0301). Likewise, patients with the T allele have a significantly lower severity of symptoms (p=0.0026) and decreased therapy effectiveness (p=0.0142) than C allele carriers.Conclusions: This study suggests that C3435T polymorphisms in the ABCB1 gene are strongly associated with a predisposition to depression development, the severity of depressive symptoms and the effectiveness of therapy with using different groups of antidepressant agents.