HLA-DR, DQ genotypes of celiac disease patients and healthy subjects from the West of Ireland

Celiac disease (CD) has one of the strongest class II HLA associations of any human illness. We used DNA-RFLP typing to study the class II HLA genotypes of celiac disease patients from the West of Ireland, the geographic area with the highest rate of celiac disease in the world. We confirmed the high frequency of HLA-DR3 in this population, and we were also able to demonstrate the additional risk of developing celiac disease imparted by HLA-DR7. This was done by clearly distinguishing DR7, DQ2 haplotypes from DR7, DQ9 haplotypes, and by "subtraction analysis" of haplotype frequencies. As reported in other populations, most of the patients without DR3 were heterozygous for DR7 and DR11 or 12 (DR5), or had DR4. We used PCR-RFLP and direct sequencing of amplified DNA to examine HLA-DR4 subtypes. The frequency of HLA-DR4 was markedly decreased in patients compared with controls (p=0.000001) and there was a significant alteration of DR4 subtypes of the patients compared with controls (p=0.0227). Moreover, all of the CD patients (5 of 5) with DR4 had a haplotype associated with the DQB1*0302 allele compared with only 11 of 23 control subjects with DR4. Our results in this population with exceptionally high risk of CD strongly support the DQ heterodimer hypothesis and suggest that the recently described sequence difference between the DQB1*02 alleles of DR3 and DR7 may contribute to a synergistic increased risk when these haplotypes are inherited together. In addition, our findings suggest a role for HLA-DQ in DR4-associated CD.     

Angiotensinogen gene M235T polymorphism is not associated with diabetic nephropathy

BACKGROUND.: There is agreement that a family history of hypertension (HT),is a predictor for the risk of diabetic nephropathy (DN) inpatients with type 2 diabetes, and possibly also type 1 diabetes.It follows that genes related to the risk of hypertension mustalso be considered candidate genes for DN. The 235T allele ofthe angiotensinogen gene was found to be related to primaryHT. METHODS.: To examine whether it is predictive for DN as well, we examinedthe angiotensinogen gene polymorphism in 230 healthy local controls,423 patients with type 1 diabetes (n=180 with DN; n=243 withoutDN) and 663 patients with type 2 diabetes (n=310 with DN; n=353without DN). The angiotensinogen gene M235T polymorphism wasdetermined using PCR amplification. RESULTS.: The following results were obtained (i) no significant differenceof genotype distribution (type 1: MM/MT/TT(%) 27.6/57.2/15.2vs. 27.2/56.1/16.7 (P=0.92); type 2: MM/MT/TT (%) 31.7/48.2/20.1vs. 32.9/46.8/20.3 (P=0.93)) or allele frequencies (type 1:M 0.56 vs. 0.55 (P=0.795); type 2: M 0.56 vs. 0.56 (P=0.86))was found, between diabetic patients with or without DN, (ii)no difference was found between normotensive and hypertensivediabetic patients. CONCLUSION.: The data argue against a role of the angiotensinogen gene M235Tpolymorphism in the manifestation of diabetic nephropathy orhypertension in diabetic patients.     

Extensive allelic sequence variation in the J region of the human immunoglobulin heavy chain gene locus

During the initial stages of B lymphocyte differentiation heavy chain variable (VH), diversity (DH) and joining (JH) gene segments recombine to form a functional heavy chain variable region (VDJ) gene. Evidence for genetic polymorphism of the human JH gene segments has been obtained from mature rearranged VDJ sequences. We conducted an analysis of the published rearranged JH gene sequences and found that the JH alleles present in the two published germ-line JH region sequences were rare (approx. 2%) in the rearranged sequences. As an attempt to explain this discrepancy a 2.5-kb strech of DNA containing all the six heavy chain JH region genes and the most 3' DH gene segment, DHQ52, was amplified by the polymerase chain reaction from 39 individuals and analyzed for restriction fragment length polymorphism. Five new JH region haplotypes were found and sequenced. These new haplotypes contained the coding segment alleles that were frequent in antibody genes. Surprisingly, a high number of interallelic differencies in the non-coding sequence was found between the new and the two previously published haplotypes implying that the haplotypes had been separated early in evolution. In this respect the JH locus resembles HLA loci.     

卡马西平多晶型的研究

红外吸收图谱与中国药典图谱不符合的卡马西平（Ａ晶），可通过用较高浓度乙醇使其转为Ｂ晶而符合规定，经￣（１３）ＣＮＭＲ、ＭＳ、Ｘ线衍射分拆，证实该两种晶体为同质异晶。     

Deleterious effect of exogenous angiotensin-I on the extent of regional ischaemia and its inhibition by captopril

The endogenous activity of the local renin-angiotensin system(RAS) and the anti-ischaemic properties of captopril were investigatedin electrically driven rabbit Langendorff hearts (constant pressure:70 cmH₂O, Tyrode solution, Ca²⁺ 1.8 mmol.l^–1). Cumulativeconcentration-response curves showed no significant difference(P>0.05) between the reduction of the global coronary flow(CF) by exogenous angiotensin-I or angiotensin-II (EC₅₀ = 10^–10mol.l^–1). It is concluded that the local RAS in isolatedrabbit hearts is highly sensitive, whereas its endogenous activityis very low due to very low endogenous angiotensin-I content.Myocardial ischaemia (MI) was induced by the occlusion of aleft coronary artery branch and MI was quantified from NADHsurface fluorescence photography. MI was significantly enlarged(+35%) (P <0.05) by exogenous angiotensin-I (6x10^–9mol.l^–1). The reduction in CF and the increment in MIby angiotensin-I could be completely prevented by adding captoprilat a low concentration (10^–6 mol.l^–1) to the perfusionbuffer. In the absence of exogenous angiotensin-I, captoprilalone (10^–6 mol.l^–1) neither significantly enhancedCF (P >0.05), nor diminished MI (P >0.05), supportingthe finding of very low endogenous activity of tile local RASin this model. We, moreover, conclude that at a low concentration(10^–6 mol.l^–1) captopril does not possess directcardioprotective properties independent of its ACE inhibitingaction.     

羧酸酯酶1和羧酸酯酶2基因表达量与体质量指数的关系及其基因多态性分析

目的 通过检测健康志愿者的羧酸酯酶1 (carboxylesterase 1,CES1)和羧酸酯酶2 (carboxylesterase 2,CES2)的基因多态性和基因表达水平,探索CES1和CES2在代谢中的作用。方法 从48例健康志愿者获得血样并提取DNA,对DNA进行二代基因测序,并提取总RNA检测基因表达量。使用多元线性回归分析CES1和CES2基因表达量与性别、年龄、体质量指数(body mass index, BMI)的关系。结果 CES1的基因表达量为141.8(72.7,237.8),CES2的基因表达量为74.4(30.8,133.6)。多元线性回归分析中,BMI与CES2的基因表达有关,性别、年龄和BMI与CES1的基因表达无关。发现CES1 20个基因变异,其中10个会引起氨基酸序列改变;发现CES2 6个基因变异,其中2个引起氨基酸序列改变。结论 发现CES2的表达水平与BMI相关,CES1的表达水平与BMI无明显相关,基因预测结果提示CES1的遗传变异可能影响其功能表达。     

ACAT-1 rs1044925单核苷酸多态性与急性冠脉综合征及阿托伐他汀治疗后血脂反应的关系研究

背景 既往研究显示ACAT-1 rs1044925单核苷酸多态性（SNP）与冠心病及缺血性脑卒中的发病风险相关,并且与血脂水平有关。目的 本研究旨在探讨ACAT-1 rs1044925 SNP与急性冠脉综合征（ACS）的关系,以及rs1044925 SNP与ACS患者阿托伐他汀治疗后调脂效果的关系。方法 选择2016年1月—2018年1月在广西壮族自治区人民医院老年心血管内科确诊为ACS并接受经皮冠状动脉介入治疗（PCI）的患者111例作为ACS组（男67例,女44例）;患者均接受阿托伐他汀治疗,20 mg/晚;同时服用氯吡格雷75 mg,1次/d（或替格瑞洛90 mg,2次/d）,阿司匹林100 mg,1次/d;并在经PCI后常规使用阿托伐他汀,20 mg/晚。对照组为同期体检健康人群,共338例（男170例,女168例）。通过聚合酶链反应和限制性片段长度多态性（PCR-RFLP）对ACAT-1 rs1044925 SNP进行基因分型,检测ACS组和对照组的基线血脂水平,随访检测ACS组患者阿托伐他汀治疗1年后血脂参数。结果 ACS组和对照组受检者的血清总胆固醇（TC）间差异无统计学...     

中国江苏地区汉族人群肿瘤坏死因子β遗传多态性研究

目的　探讨中国江苏地区汉族人群肿瘤坏死因子 β遗传多态性分布。方法　收集江苏地区 16 8名无血缘关系健康个体的静脉血提取DNA ,应用聚合酶链反应限制性片段长度多态性 (PCR -RFLP) ,对TNFβ基因多态性进行分析。结果　TNFβ检测到三个等位基因 ,其基因型频率分别为TNFβ 1/ 1=2 1 4 % ,TNFβ 1/ 2 =4 7% ,TNFβ 2 / 2 =31 5 % ,基因型分布符合Hardy-Weinberg定律。统计分析显示 :江苏地区汉族人群TNFβ等位基因频率分布与欧美白种人均有显著性差异(P <0 0 5 )。结论　TNFβ等位基因频率分布具有种族差异     

Genetic polymorphism of CCR5 gene and HIV disease: The heterozygous (CCR5/Δccr5) genotype is neither essential nor sufficient for protection against disease progression

Homozygous (Δccr5/Δccr5) and heterozygous (CCR5/Δccr5) deletions in the β-chemokine receptor 5 (CCR5) gene, which encodes for the major co-receptor for macrophage-tropic HIV-1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/Δccr5 genotype was found more frequently in long-term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan-Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4⁺ T cell counts >500/μl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/Δccr5 genotype. However, when LTNP were analyzed separetely, no significant differences in CD4⁺ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild-type (69 % of LTNP) and the heterozygous (31.0 %) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/Δccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/Δccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.