CYP19a1基因的单核苷酸多态性与中国汉族成人寻常痤疮的关联研究

目的:初步探索CYP19a1基因的单核苷酸多态性(SNP)与中国汉族成人寻常痤疮发病和严重程度的关系。方法:共纳入309例Pillsbury分级Ⅰ~Ⅳ的寻常痤疮患者,分为轻度组(Ⅰ级,99例)和中重度组(Ⅱ~Ⅳ级,210例)。从患者外周静脉血中抽提DNA组,经多重聚合酶链式反应(PCR)获取目的基因片段后,采用SNa Pshot分型技术检测CYP19a1基因上的10个候选SNP位点的基因型。结果:1 rs28892002位点在显性遗传模式下,CC基因型的分布频率在中重度组显著高于轻度组(58.5%vs.46.5%,P=0.046,OR=0.614,95%CI=0.379~0.993);2 rs2255192-rs4646-rs10064-rs700519这组单倍型在显性模式下,其C-C-CC、C-C-T-C基因型在两组间分布差异有统计学意义(P值分别为0.0000、0.0216,OR值分别为5.0198和2.0707)。结论:中国汉族人群中,CYP19a1基因上的rs28892002位点CC野生纯合子基因型可能增加中重度寻常痤疮的患病风险;rs2255192-rs4646-rs10064-rs700519这组单倍型在显性模式下,其C-C-C-C、C-C-T-C基因型可能减少中、重度寻常痤疮的患病风险。     

CYP2B6基因多态性与异维A酸人体代谢动力学差异关联性研究

目的 探讨细胞色素P450（CYP2B6）基因多态性与异维A酸人体代谢动力学的关系。方法21例健康受试者单次口服40mg异维A酸胶丸（商品名泰尔丝）,提取外周血基因组DNA进行PCR及限制性核酸内切酶片段分析方法（RFLP）分析CYP2B6第四外显子exon4及第五外显子exon5基因分型。高效液相色谱-质谱法（LC/MS）分析受试者异维A酸血药浓度并计算相关药动学参数。结果 21例健康受试者CYP2B6 exon4及exon5存在明显的连锁不平衡性。等位基因CYP2B6*4野生型*1/*1为12例（57.14%）,杂合型*1/*4为6例（28.57%）,突变型*4/*4为3例（14.29%）;等位基因CYP2B6*6野生型*1/*1为13例（61.90%）,杂合型*1/*6为5例（23.81%）,变异型*6/*6为3例（14.29%）。等位基因CYP2B6*4野生型体内消除参数t1/2及MRT高于突变型（P值均 < 0.05）,吸收参数Cmax、Tmax及AUC等两组差异无统计学意义。等位基因为CYP2B6*6的野生型与突变型各项药动学参数差异均未见有统计学意义（P > 0.05）。 结论 代谢酶CYP2B6等位基因*4突变与异维A酸体内代谢相关。CYP2B6*4突变型可能为异维A酸快代谢型人群。     

CYP17基因多态性与痤疮中医分型的相关性

目的探讨CYP17基因多态性与痤疮中医分型的相关性。方法提取肝郁气滞型、湿热内蕴型痤疮患者和正常对照者的血DNA标本。设计引物通过PCR技术扩增出包括CYP17基因多态位点的片段,用限制性内切酶Ms- pA1Ⅰ进行酶切,产物在2%琼脂糖凝胶上电泳,确定出CYP17基因的3种基因型(A1A1、A1A2、A2A2),并经测序证实。结果肝郁气滞型组基因型A1A2频率、湿热内蕴型组基因型A1A2频率间及分别与正常对照组基因型A1A2频率比较,差异无显著性意义(P>0.05);肝郁气滞型组基因型A2A2频率和正常对照组基因型A2A2频率比较,差异无显著性意义(P>0.05);湿热内蕴型组基因型A2A2频率分别与肝郁气滞型组基因型A2A2频率和正常对照组基因型A2A2频率比较,差异有显著性意义(P<0.05)。结论CYP17基因-34bp处T→C碱基的置换存在与痤疮湿热内蕴型有关。     

良性前列腺增生TURP术后尿路感染病原菌特征、耐药性及与CYP1A2基因多态性的关系研究

目的研究良性前列腺增生(BPH)经尿道前列腺切除术(TURP)术后尿路感染病原菌特征、耐药性及与细胞色素P450酶1A2(CYP1A2)基因多态性的关系。方法选取2016年1月至2020年12月浙江省玉环市人民医院收治的234例行TURP治疗的BPH患者作为研究对象。根据术后有无尿路感染分为感染组(n=36)和非感染组(n=198),分析尿路感染病原菌和耐药性,检测CYP1A2基因多态性,采用Logistic回归分析CYP1A2基因多态性位点与TURP术后尿路感染的关系。结果36例TURP术后尿路感染患者共培养出病原菌42株,革兰氏阴性菌占61.90%,革兰氏阳性菌占28.57%,真菌占7.14%,其中主要以大肠埃希菌为主,占35.71%;大肠埃希菌对氨苄西林、环丙沙星、左氧氟沙星、庆大霉素的耐药率较高,均>60.00%。感染组CYP1A2基因Rs762551位点AA基因频率及A等位基因频率高于非感染组,CC基因频率及C等位基因频率低于非感染组(P<0.05);两组CA基因频率比较,差异无统计学意义(P>0.05)。Logistic回归分析显示,CYP1A2基因Rs762551位点AA基因型(OR=3.991,95%CI:1.251~12.735)发生TURP术后尿路感染的风险显著升高(P<0.05)。结论BPH患者TURP术后尿路感染以大肠埃希菌为主,且CYP1A2基因Rs762551位点AA基因型可增加TURP术后尿路感染的风险。     

雷公藤多甙联合低分子肝素/氯吡格雷治疗青斑样血管病10例

目的评价雷公藤多甙片(GTT)联合低分子肝素针(LMWH)/氯吡格雷片治疗青斑样血管病(LV)的临床疗效和安全性。方法对常规治疗效无效的10例LV患者,予GTT片联合LMWH/氯吡格雷片治疗(强化期:GTT片20mg口服,2~3次/d,低分子肝素0.3m L皮下注射,1次/d。维持期:GTT片10mg口服,2~3次/d,氯吡格雷75mg口服,隔日1次)。随访3个月~1年。结果强化治疗2周后,6例溃疡开始愈合,疼痛消失;治疗6周后,8例溃疡愈合。疗程中均不良反应少且轻微。结论雷公藤多甙片联合低分子肝素针/氯吡格雷片对于常规治疗疗效差的青斑样血管病安全有效。     

以缺血性脑卒中为主要症状的HIV阴性神经梅毒患者的临床分析

目的研究以缺血性脑卒中为主要症状的HIV阴性神经梅毒患者的临床特点,提高对该病的认识,减少临床误诊。方法回顾性分析98例神经梅毒患者。对照组包括16名非神经梅毒缺血性脑卒中患者。分析缺血性脑卒中作为不同类型神经梅毒的主要症状,神经梅毒缺血性脑卒中误诊率的比例,以及与相关危险因素的关系。结果 98例神经梅毒患者中,12例发生缺血性脑卒中为主要症状,其中1例为脑膜炎型神经梅毒,11例为脑膜血管型神经梅毒。神经梅毒缺血性脑卒中患者中只有2名有卒中史,其它10例均在随访治疗期间被诊断为神经梅毒,误诊率高达83.33%。此外,除高血压外,两组间心血管危险因素无显著差异(P>0.05)。结论在临床实践中,特别是在紧急情况下,任何缺血性脑卒中患者都应进行神经梅毒筛查。     

急性缺血性脑卒中患者脱水状态对静脉溶栓预后影响

目的 探究脱水状态对部分前循环梗死(PACI)型急性缺血性脑卒中静脉溶栓患者预后影响,为临床早期判断脑卒中预后提供依据.方法 选取2017年1月—2019年8月湖北医药学院附属国药东风总医院收治的78例急性缺血性脑卒中患者,患者均接受阿替普酶静脉溶栓治疗.根据阿替普酶静脉溶栓前患者血尿素氮/肌酐(BUN/Cr)比值将患...     

ABCD2评分诊断急诊头晕患者脑卒中风险的ROC曲线研究

目的研究ABCD2评分诊断急诊头晕患者脑卒中风险的价植。方法以2014年4月-2018年4月上海市第六人民医院东院急诊室收治的372例头晕患者为对象,开展回顾性分析。统计患者一般资料,均行ABCD2评分系统评估,观察头晕患者脑卒中发生情况,分析ABCD2评分对头晕患者脑卒中的预测能力,并分析其与脑卒中患者预后的关系。结果372例头晕4者中,有69例(18.55%)发生脑卒中,其中脑梗死66例(95.65%),出血性脑梗死3例(4.35%),均纳为脑卒中组;其余303例(81.45%)未发生脑辛中,纳为非脑卒中组。脑卒中组年龄>60岁、血压>140/90 mmHg、单侧肢体无力、症状持续时间>60 min、糖尿病所占比例均显著高于非脑卒中组(P0.05)。结论ABCD2评分能有效评估头晕患者脑卒中风险,临床应引起足够重视。     

急性脑卒中与低钠、低氯血症关系及其临床意义

目的 探讨低钠、低氯血症与急性脑卒中的病情轻重、卒中类型及其预后的关系.方法 2005年6月至2006年12月我院收治的符合入选条件的急性脑卒中患者412例(出血性卒中179例,缺血性卒中233例),于入院次日、7天、14天晨检测空腹血钠、血氯.入院后24 h内对患者的病Eainburgh-Scandinavia临床神经功能缺损程度评分标准进行评分,并分为轻型184例,中型145例,重型83例.结果 出血性卒中组低钠、低氯血症的发生率明显高于缺血性卒中组;低钠、低氯血症组中的中、重度患者显著多于正常血钠、血氯组;低钠、低氯血症组死亡率也明显高于正常血钠、血氯组.差异均有统计学意义.结论 低钠、低氯血症可以作为判断急性脑卒中病情、预后评估的指标.     

斑秃与人类白细胞抗原-DQB1~*03等位基因相关

斑秃(AA)是一种自身免疫性或免疫介导性疾病,与特定的主要组织相容性复合物(MHC)Ⅱ类等位基因明显相关。作者使用聚合酶链反应(PCR)技术结合等位基因特异的寡核苷酸(SSO)探针杂交对一组美国白人AA患者作人类白细胞抗原(HLA)-DQA1,-DQB1,-DPB1等位基因分型,同时对38例DR4和23例DR5(DRB1~*11)阳性的AA患者分亚型,以了解HLA基因在AA及全秃/普秃(AT/AU)易感性或抗性中的作用。     

Association of the CYP17 MSP AI (T‐34C) and CYP19 codon 39 (Trp/Arg) polymorphisms with susceptibility to acne vulgaris

The aim of this study was to detect the association of the cytochrome P450 (CYP) 17 T‐34C and CYP19 T<C polymorphisms with the risk of acne vulgaris (AV). The study enrolled 198 patients with AV (mild, moderate and severe) and 195 unrelated age‐matched healthy controls from western Iran who had Kurdish ethnic background. The presence of the CYP17 TC genotype significantly increased the risk of mild, moderate and severe AV by 2.68, 2.28 and 2.94 times, respectively, while the presence of the CYP19 TC genotype significantly elevated the risk of overall AV and mild AV by 2.1 and 3.2 times, respectively. There was a synergy between the CYP 17 TC and CYP19 TT genotypes, which increased the risk of AV by 2.45‐fold (P < 0.001). To our knowledge, this is the first study showing that the CYP17 T‐34C and CYP19 T<C variants and their synergy are associated with susceptibility to AV in an Iranian population.     

HLA Cw*06 is not essential for streptococcal-induced psoriasis

BACKGROUND: Streptococcal throat infections and HLA Cw6 (Cw*06) have been implicated in the pathogenesis of psoriasis, particularly in the guttate form. OBJECTIVES: To study 105 Irish patients with psoriasis to investigate the relationship between streptococcal infections and Cw*06. METHODS: The patients were divided into two groups: those with guttate psoriasis or guttate flare (guttate group, GG, n=64) and those with chronic plaque psoriasis (chronic plaque group, CPG, n=41). RESULTS: The incidence of Cw*06 was 86% in the GG and 73% in the CPG, which was not significantly different (P=0.1725) but the incidence in both groups was significantly higher than in an Irish control group (18%) (P<0.0001 vs. GG and P<0.0001 vs. CPG). Evidence for streptococcal infection was higher in the GG (56%) than in the CPG (32%) (P=0.0231). Of those patients with evidence of streptococcal infection, 30 of 36 GG (83%) and nine of 13 CPG (69%) patients possessed the Cw*06 genotype. CONCLUSIONS: Thus, not all patients with streptococcal-related psoriasis carry Cw*06. The role of Cw*06 in psoriasis, if any, has yet to be determined.     

Cytochrome P450 polymorphisms in patients with Behcet's disease

OBJECTIVES: Although the etiopathogenesis of Behcet's disease (BD) remains unknown, increased neutrophil functions such as chemotaxis, phagocytosis and excessive production of reactive oxygen species, including superoxide anion, may be responsible for the oxidative tissue damage observed in BD. Cytochrome P-450 are a multigene family of enzymes involved in the detoxification and occasional activation of a wide variety of chemicals. Our aim was to investigate CYP2C9 and CYP2C19 polymorphisms in patients with BD. METHODS: Sixty-two subjects with BD and 107 healthy control subjects were enrolled in the study. Polymorphisms of CYP2C9 and CYP2C19 were performed by real-time PCR with a LightCycler instrument. We researched associations between CYP polymorphisms and BD. RESULTS: The frequencies of wild-type and heterozygous CYP2C19*2 genotypes were 66.1% and 33.9% in the patients and 83.2% and 16.8% in the controls, respectively. There was a 2.53-fold increased risk of Behcet's disease in individuals with the CYP2C19*2 heterozygous genotype (OR = 2.53; 95% CI, 1.22-5.25) when compared with the control group. But the CYP2C9*2, CYP2C9*3 and CYP2C19*3 gene polymorphisms were not related to an increased risk of developing BD. CONCLUSIONS: We observed that patients with BD presented with a higher prevalence of the heterozygous CYP2C19*2 genotype. Hereditary deficiencies of this enzyme activity may lead to an imbalance between pro- and antioxidant systems, resulting in the formation of excessive reactive oxygen species.     

华东地区汉族斑秃与HLA-DRB1*03、*04、*11基因多态性的关联研究

目的 探讨中国华东地区汉族人群HLA-DRB1基因与斑秃发病、临床特点的关系。方法 采用序列特异性引物PCR（PCR-SSP）技术对已确诊为斑秃的158例和正常人对照组172例进行HLA-DRB1基因多态性分析。并比较斑秃患者不同发病年龄、发病次数、病程、家族史及严重程度与HLA-DRB1基因的关联性。结果 斑秃组HLA-DRB1*03、HLA-DRB1*11等位基因频率与对照组差异无统计学意义。斑秃组HLA-DRB1*04（OR = 1.99,Pc = 0.01）等位基因频率明显高于对照组。与正常人对照组比较,斑秃晚发组（发病年龄 > 16岁）（OR = 1.94,Pc = 0.02）、斑秃复发组（发病次数 > 1）和初发组（OR = 2.49、Pc = 0.02,OR = 1.83、Pc = 0.04）、病程 > 1年的患者（OR = 2.94,Pc = 0.01）、无家族史的患者（OR = 1.97,Pc = 0.02）、严重斑秃患者（OR = 3.53,Pc = 0.00）HLA-DRB1*04等位基因频率均显著升高。结论 中国华东地区汉族人群HLA-DRB1*04等位基因与斑秃发病、临床分型显著相关。     

过敏性紫癜与子宫珠蛋白基因多态性的相关性研究

目的 探讨子宫珠蛋白基因多态性与过敏性紫癜、紫癜性肾炎发病易感性和临床、病理表型的联系。方法 过敏性紫癜患儿118例,包括80例肾炎患者（紫癜性肾炎患者）和38例无肾炎患者,正常儿童100例。提取静脉血白细胞基因组DNA, PCR－RFLP法确定子宫珠蛋白基因G38A基因型。用χ2检验比较各组子宫珠蛋白不同基因型频率及不同基因型的紫癜性肾炎患者临床和肾脏病理特征。结果过敏性紫癜各组分别与正常对照组比较,肾炎组与无肾炎组比较,子宫珠蛋白基因3种基因型（38GG、38AG、38AA）频率差异无统计学意义（P > 0.05）。三种基因型与过敏性紫癜四种临床表型以及紫癜性肾炎患者肉眼血尿、肾病综合征等临床表型和肾脏病理损害等级无关（P > 0.05）。过敏性紫癜伴血清IgE增高组38AA型频率较血清IgE正常组明显升高（χ2 ＝ 21.95,P < 0.01,OR = 15.51,95％ CI为4.93 ～ 48.84）。紫癜性肾炎伴高血压组38GG型频率较无高血压组显著升高（χ2 ＝ 26.17,P < 0.01,OR = 13.61,95％ CI为5.01 ～ 37.01）。结论 子宫珠蛋白基因G38A多态性与过敏性紫癜、紫癜性肾炎易感性及肾脏病理损害程度无关,而子宫珠蛋白基因38AA型的过敏性紫癜患者可能容易出现血清IgE增高,38GG型的紫癜性肾炎患者可能容易出现高血压。     

Association of CYP2C9 Genetic Variants with Vitiligo

Background

Vitiligo is a depigmenting skin disorder in which genetic factors play an important role.

Objective

To examine the association of CYP2C9 ^*1/^*2/^*3 gene polymorphism with vitiligo.

Methods

In this case controlled study, 95 Saudi patients with vitiligo (50 men and 45 women), with a mean age of 27.3 years, were analyzed. Patients were compared to 86 healthy controls from the same locality (76 men and 10 women), with a mean age of 20.1 years. In all participants, DNA was extracted and processed for characterization of 2C9 ^*1/^*2/^*3 gene variants using real time-polymerase chain reaction.

Results

Vitiligo patients have a significantly higher CYP2C9 ^*3 allele carriage rate compared to controls (32.7% versus 4.7%, p=0.00, odds ratio=9.9, 95% confidence interval=3.3~29.6). On the other hand, frequencies of CYP2C9 ^*2 genotypes and alleles did not show any significant difference between vitiligo cases and controls. When the frequencies of CYP2C9 genotypes were compared among subgroups of age, gender, family history, and disease patterns, the cases with positive consanguinity had significantly higher frequencies of homozygous genotypes than others (p=0.029).

Conclusion

CYP2C9 ^*3 allele carriage is probably associated with vitiligo susceptibility.     

TAP-1等位基因多态性与复发性尖锐湿疣间的关系

目的 探讨TAP-1333、TAP-1637基因多态性与中国人群复发性尖锐湿疣（CA）的关系。方法 采用扩增阻滞突变系统-聚合酶链反应（ARMS-PCR）技术检测88例复发性CA患者和81例正常人对照者TAP-1333基因位点的A/G单核苷酸多态性，以及60例复发性CA患者和60例健康对照者（对照组）TAP-1637基因位点的A/G单核苷酸多态性。结果 CA组TAP-1333等位基因AA、GG、AG基因频率分别为86.36%、0%和13.64%，对照组各等位基因频率分别为79.01%、0%和20.99%，组间差异无统计学意义（χ2 = 1.604，P ＞ 0.05），OR值 ＝ 1.682（0.748 ~ 3.783）。CA组TAP-1637等位基因AA、GG、AG基因频率分别为3.33%、95.00%和1.67%，而对照组各等位基因频率分别为10.00%、60.00%和30.00%,在CA组，天冬氨酸（Asp）杂合型和纯合型出现频率明显低于对照组，而甘氨酸纯合型明显高于对照组，组间差异有统计学意义（χ2 = 23.682，P ＜ 0.01）。AA型：OR值 = 0.310（0.060 ~ 1.604）；GG型：OR值 = 12.667（3.555 ~ 45.135）；AG型：OR值 = 0.04（0.005 ~ 0.308）。结论 TAP-1333位点基因多态性与复发性CA无关；TAP-1637基因位点多态性可能与复发性CA有相关性。     

Gene-wide association study between the aromatase gene (CYP19A1) and female pattern hair loss

Background  Female pattern hair loss (FPHL) is a common trait in which androgens and oestrogens may have a pathogenic role. The aromatase enzyme converts androgens to oestrogens in scalp hair follicles and is differentially expressed in balding and nonbalding scalps of women. Sequence variation in the gene encoding aromatase, CYP19A1 , might influence the risk of developing FPHL.
Objectives  To examine the role of CYP19A1 genetic variation in the heritability of FPHL.
Methods  We investigated associations between FPHL and 61 tag single nucleotide polymorphisms (SNPs) representing variation in and around CYP19A1 in 484 caucasian women with grades 3–5 FPHL on the Sinclair scale, and 471 caucasian women with no evidence of hair loss.
Results  For the tag SNP rs4646 (overall genotype frequencies: CC, 53·6%; AC, 39·3%; AA, 7·1%), the genotype CC was more frequent in women with FPHL (58·1%) than controls (48·9%) ( P  =   0·006). Although this result did not achieve experiment-wide significance ( P  <   0·001 by permutation testing), subanalyses according to sources of recruitment and ages at presentation revealed consistent patterns of association. In particular, young cases (< 40 years) had the highest frequency of the CC genotype (68·2%) among all subgroups.
Conclusions  These findings suggest that the common rs4646 C allele, which has been associated previously with higher circulating oestrogen levels, might be associated with predisposition to FPHL.