壮族冠心病患者的TLR4表达水平及其rs4986790A/G、rs4986791C/T位点的多态性分析

目的探讨广西壮族冠心病(CHD)患者的TLR4蛋白表达水平及其rs4986790A/G、rs4986791C/T位点的多态性。方法选取2016年1月至2018年1月在我院行冠状动脉造影(CAG)检查被确诊为CHD的壮族患者245例为CHD组,选取同期在我院住院治疗的245例非CHD患者为对照组。采用酶联免疫吸附法(ELISA)检测两组患者的血清TLR4蛋白表达水平;采用SNaPshot测序技术检测两组患者外周血TLR4基因rs4986790A/G、rs4986791C/T位点的基因型及等位基因。分析TLR4蛋白表达水平及其rs4986790A/G、rs4986791C/T位点的多态性与壮族人群CHD发病的相关性。结果 CHD组患者的外周血TLR4蛋白表达水平高于对照组,差异有统计学意义(P0.05)。CHD组患者的TLR4基因rs4986790A/G、rs4986791C/T位点的等位基因及基因型频率分布与对照组患者比较,差异无统计学意义(P0.05)。结论外周血TLR4蛋白表达水平与广西壮族人群CHD的发生存在关联,但TLR4基因rs4986790A/G、rs4986791C/T位点的多态性可能与壮族人群CHD冠心病发病无明显的相关性。     

广西壮族人群SLC2A9基因多态性位点与原发性痛风的关联性研究

［摘要］　目的　探讨广西壮族人群可溶性载体2家族成员9（SLC2A9）基因单核苷酸多态性（SNPs）与原发性痛风的关联性。方法　收集广西壮族人群246例原发性痛风患者和202名健康对照者的临床资料及血尿酸（UA）、空腹血糖、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）、肌酐（Cr）、尿素氮（BUN）等实验室指标,比较两组临床及实验室指标的差异。Taqman-MGB探针法检测SLC2A9基因4个位点(rs10489070、rs734553、rs3733591、rs16890979)的基因型,比较两组基因型及等位基因分布频率。结果　痛风组的体质量指数（BMI）、TG、TC、LDL-C、Cr、UA水平显著高于对照组（P<0.05）。有痛风石的患者年龄更大,病程更长,累及关节数更多,肾结石发生率更高,TG、TC、LDL-C、Cr、UA水平更高,差异均有统计学意义（P<0.05）。rs10489070和rs3733591在痛风组与对照组基因型及等位基因分布频率差异有统计学意义（P<0.05）,携带C等位基因的个体发生痛风的OR值分别为1.413（95%CI：1.009～1.980）和1.739（95%CI：1.331～2.271）。rs3733591（CC）（aOR=2.113,95%CI：1.536～3.951）、rs10489070（CC）（aOR=1.981,95%CI：1.123～3.156）是痛风发生的独立危险因素。rs3733591（CC）（aOR=2.358,95%CI：1.114～3.221）、rs10489070（CC）（aOR=2.115,95%CI：1.689～4.547）是痛风石发生的独立危险因素。结论　我国壮族人群中,SLC2A9基因的rs10489070（CC）和rs3733591（CC）基因型是痛风和痛风石的独立危险因素,但目前易感位点影响痛风发病的具体机制尚不明确,下一步需要进行相关SNPs功能的研究。     

盐敏感性高血压易感基因多态性的种族差异性研究

目的 探讨HapMap数据库中四个种族人群盐敏感性高血压易感基因频率的分布差异.方法 利用HapMap数据库中犹他州的欧洲西部和北部的后裔(CEU)、中国北京汉族人(CHB)、日本东京人(JPT)以及尼日利亚的约巴鲁人(YRI)四个种族人群的基因频率数据,建立盐敏感性高血压易感基因多态性(血管紧张肽原基因多态性AGT/M235T、血管紧张素转换酶基因多态性ACE/ID、醛固酮合成酶基因多态性CYP11B2/C344T、α-内收蛋白基因多态性α-adducin/G460T、G蛋白β3亚基基因多态性GNB3/C825T和细胞色素P450 3A酶基因多态性CYP3A5/A6986G)基因数据库(n=395).应用拟合优度卡方检验验证每个基因型分布频率是否符合Hardy-Weinberg平衡定律.利用χ2检验,对不同种族盐敏感性易感基因的基因型频率和等位基因频率进行比较,并进行趋势性检验.同时,运用χ2分割方法 进行两组间的多重比较.结果 四个种族人群盐敏感性易感基因的频率分布存在统计学差异(P＜0.05＝.组间两两比较的结果 发现CHB与JPT人群间的基因型和易感等位基因频率分布没有显著性差异.除了GNB3/825T等位基因频率没有显著性差异(38.8%比34.4%,P=0.521)外,与CEU人群相比,CHB人群的AGT/235T(79.2%比41.2%,P＜0.001＝、ACE/I(56.5%比43.5%,P＜0.001＝、CYP11B2/-344T(74.1%比56.7%,P=0.001)、ADDI/460Trp(51.8%比20.4%,P＜0.001＝和CYP3A5/A6986(30.1%比3.6%,P＜0.001＝等位基因突变频率明显偏高.ADDI/460Trp等位基因在YRI群中分布极低,仅为4%,明显低于CHB人群(51.8%,P＜0.001＝,而AGT/235T、CYP11B2/-334T、GNB3/825T、CYP3A5/6986A基因多态性突变频率均显著地高于CHB人群.根据CEU、CHB、YRI三个人群的趋势性检验的结果 发现,AGT/235T(41.2%＜79.2%＜92.0%,P＜0.001＝、CYP11B2/-334T(56.7%＜74.1%＜84.8%,P＜0.001＝和CYP3A5/6986A(3.6%＜30.1%＜84.5%,P＜0.001＝三个盐敏感性易感基因所携带的突变等位基因型频率呈现显著增加趋势.结论 利用HapMap数据库提供的四个种族基因多态性检测数据进行分析的结果 提示我们,盐敏感性高血压易感基因多态性在不同种族人群中的分布具有显著性差异.北京汉族人群盐敏感性易感等位基因的频率近似于JPT人群,高于CEU人群而低于YRI人群,说明北京汉族人群有较高的盐敏感性,针对高危人群进行预防和个体化治疗将有助于降低盐敏感性高血压和心血管疾病的发生.     

TCF7L2基因rs7903146T/C和rs7901695T/C单核苷酸多态性与内蒙古汉族人群2型糖尿病易感性的相关性研究

目的研究内蒙古地区汉族人群中T2DM易感性与TCF7L2基因rs7903146T/C和rs7901695T/C位点单核苷酸多态性(SNPs)是否相关。方法收集T2DM患者和正常体检人群的抗凝血,采用等位基因特异性PCR(AS-PCR)进行SNPs分析;运用SHEsis软件对T2DM组和正常对照(NC)组的TCF7L2基因的SNPs位点进行连锁不平衡和单倍型分析。结果rs7903146T/C和rs7901695T/C位点的基因型分布在T2DM及NC组间的分布差异无统计学意义(P>0.05),但rs7903146T/C位点的T和C等位基因频率在两组间的分布差异有统计学意义(P<0.05)。rs7903146T/C和rs7901695T/C位点连锁平衡(D′=0.060),rs7901695T-rs7903146T单倍型在T2DM组的频率明显高于NC组(P<0.01,OR=1.803,95%CI:1.183～2.7487)。结论在内蒙古地区汉族人群,rs7903146位点C→T多态性可能与T2DM关联,携带突变等位基因T可增加罹患T2DM的风险,rs7901695位点C→T多态性与T2DM易感性无明显相关性,但rs7901695T-rs7903146T单倍型与T2DM发病风险相关。     

核黄素转运蛋白C20orf54基因rs3746804位点单核苷酸多态性与食管鳞癌遗传易感性的关系

  目的 探讨核黄素转运蛋白C20orf54基因外显子3中rs3746804位点单核苷酸多态性（SNP）与食管鳞癌（ESCC）遗传易感性的关系。方法 磁珠法提取全血基因组DNA,以直接测序方法对434例包括长治、林州两地ESCC患者与554例包括长治、林州健康人群及由林州移居长治的健康移民5组人群的C20orf54基因外显子3的SNP1139C>T进行基因分型。结果 长治ESCC组与长治健康组、健康移民组在基因型CT(37.5%比51.0%、37.5%比52.0%)、CC(44.2%比34.8%、44.2%比33.0%)的分布频率上差异明显（P值均<0.05）,与林州ESCC组在基因型TT(18.3%比4.1%)、CC(44.2%比54.6%)的分布频率上有明显差异（P值均<0.05）;林州ESCC组与健康移民组在基因型TT(4.1%比15.0%)、CT(41.2%比52.0%)、CC (54.6%比33.0%)的分布频率上差异明显（P值均<0.05）,与长治健康组在基因型TT(4.1%比14.1%)、CC(54.6%比34.8%)的分布频率上差异明显（P值均<0.01）。肿瘤组（长治ESCC组+林州ESCC组）与健康组（长治健康组+林州健康组+健康移民组）在基因型CT(39.2%比48.7%)和CC (48.8%比38.2%)的分布频率上差异明显（P值均<0.01）。相对于CC基因型,CT和CT+TT基因型可以降低食管癌发生的危险性（OR=0.630,95%CI 0.481~0.826;OR=0.654,95%CI 0.507~0.844）。结论 C20orf54基因外显子3中rs3746804 位点的SNP与食管鳞癌的遗传易感性明显相关。     

rs3804100、rs3804099及rs2295080基因多态性与黑龙江省2型糖尿病患者并发肺结核关系的研究

目的探究Toll样受体2(Toll-like receptor 2,TLR2)rs3804100、rs3804099位点和哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)rs2295080位点基因多态性与2型糖尿病并发肺结核的关系。方法选择2017年1-9月黑龙江省传染病防治院收治的300例2型糖尿病并发肺结核患者作为观察组,以及同时期在哈尔滨医科大学附属第四医院内分泌科就诊的300例2型糖尿病患者作为对照组。所有患者收集血液提取DNA,用PCR技术对TLR2的rs3804100、rs3804099位点及mTOR的rs2295080位点进行基因多态性检测,并对这3个基因位点多态性与2型糖尿病并发肺结核的关系进行单因素和logistic多因素分析。结果单因素分析结果显示,TLR2的rs3804100位点TT、TC、CC(T:胸腺嘧啶;C:胞嘧啶)基因型在观察组和对照组分布构成比分别为51.3%(154/300)、25.7%(77/300)、23.0%(69/300)和47.0%(141/300)、31.3%(94/300)、21.7%(65/300),差异无统计学意义(χ^2=2.382,P=0.304);TLR2的rs3804099位点TT、TC、CC基因型在观察组和对照组分布构成比分别为53.0%(159/300)、29.7%(89/300)、17.3%(52/300)和54.3%(163/300)、33.0%(99/300)、12.7%(38/300),差异无统计学意义(χ^2=2.759,P=0.252);mTOR的rs2295080位点TT、TG、GG(G:鸟嘌呤)基因型在观察组和对照组分布构成比分别为26.7%(80/300)、67.3%(202/300)、6.0%(18/300)和24.3%(73/300)、66.0%(198/300)、9.7%(29/300),差异无统计学意义(χ^2=2.935,P=0.231)。logistic多因素分析结果显示,TLR2的rs3804100位点TC、CC基因型的OR(95%CI)值分别为1.261(0.591~2.689)和1.284(0.542~3.042),P值分别为0.549和0.569;TLR2的rs3804099位点TC、CC基因型的OR(95%CI)值分别为0.752(0.461~1.227)和0.729(0.430~1.235),P值分别为0.254和0.240;mTOR的rs2295080位点TG、GG基因型的OR(95%CI)值分别为1.789(0.890~3.596)和1.603(0.839~3.063),P值分别为0.103和0.153。结论 TLR2基因rs3804100、rs3804099位点及mTOR的rs2295080位点多态性与黑龙江省2型糖尿病并发肺结核均无相关性。     

广东汉族人群PPARGC1A基因rs6821591和rs2970847位点单核苷酸多态性与2型糖尿病遗传易感性的关联研究

目的探讨T2DM遗传易感性与广东汉族人群PPARGC1A基因rs6821591和rs2970847位点单核苷酸多态性(SNP)的关联。方法采用病例对照设计,运用SNPscanTM分型技术检测T2DM组和正常对照组(NC)PPARGC1A基因rs6821591和rs2970847位点的基因型,比较两组基因型及等位基因频率分布。结果 NC、T2DM组rs6821591位点T、C等位基因频率分别为67.31%、32.69%/67.57%、32.43%,rs2970847为23.91%、76.09%/23.95%、76.05%,两组双位点等位基因频率分布及TT/CT/CC基因型频率分布比较,差异无统计学意义(P0.05)。调整协变量前后,两组rs6821591和rs2970847位点的隐性、显性、共显性及超显性遗传模型比较,差异无统计学意义(P0.05)。结论T2DM遗传易感性可能与广东汉族人群PPARGC1A基因rs6821591和rs2970847位点SNP无明显关联。     

磷酸二酯酶4D基因rs966221位点单核苷酸多态性与缺血性脑卒中发病的关系

目的探讨广西壮族人群磷酸二酯酶4D(PDE4D)基因rs966221位点单核苷酸多态性与缺血性脑卒中(IS)发病的关系。方法采用病例-对照研究设计,运用SNaPshot技术对101例广西壮族IS患者(IS组)及同期104例健康体检者(对照组)的PDE4D基因rs966221位点单核苷酸多态性进行检测,比较2组各基因型及等位基因频率,并进行相关性分析。结果 IS组与对照组PDE4D基因rs966221位点GG、GA、AA基因型(0.99%vs 3.85%,29.70%vs 21.15%,69.31%vs 75.00%)及G、A等位基因频率(15.84%vs 14.42%,84.16%vs 85.58%)比较,差异无统计学意义(P0.05)。单因素及多因素logistic回归分析显示,在显性(AAvs GG+GA)、隐性(GGvs AA+GA)和加性(GGvs AA)3种遗传模型下,PDE4D基因rs966221位点单核苷酸多态性与IS患病风险均无关联(P0.05)。结论广西壮族人群PDE4D基因rs966221位点单核苷酸多态性与IS发病不相关。     

中国人群MYO15A基因同义突变引起剪接异常导致的非综合征型耳聋分析

［摘要］　目的　对一个遗传性非综合征型耳聋家系的临床特征进行分析并鉴定其致聋基因突变,同时在大规模耳聋人群队列中对鉴定出的致病性突变致中国人群耳聋的特征进行分析。方法　完善家系成员的问卷调查、听力学检查、体格检査等临床检查,同时采集血液样本,通过耳聋相关基因的大规模平行测序(MPS)和生物信息学分析进行致病基因鉴定。总结及分析鉴定出的致病性突变在中国耳聋基因研究战略联盟(CDGC)耳聋数据库中的检出情况。结果　在一个早发性极重度感音神经性耳聋家系中鉴定出MYO15A基因NM_016239.4:c.8182C>G（p.Arg2728Gly）/c.9861C>T（p.Gly3287=）复合杂合突变,为该家系耳聋患者的致聋原因。其中MYO15A基因c.9861C>T（p.Gly3287=）同义突变通过改变剪接导致基因功能缺陷,其在中国广西壮族人群中次要等位基因频率为0.2%（3/1 438）,在其他人群及公共数据库中均未检出。结论　研究确定了MYO15A基因c.9861C>T（p.Gly3287=）在中国非综合征型耳聋患者中的致病性,该突变在中国广西壮族自治区富集明显。通过研究强调了在致病基因鉴定时,高频与同义突变并非过滤的绝对指标,尤其是在某些地区富集格外明显的突变,应格外注意。     

ABCB1基因多态性对慢性粒细胞白血病及胃肠道间质瘤患者治疗药物伊马替尼血药浓度影响的Meta分析

［摘要］　目的　系统性评价ABCB1基因多态性对慢性粒细胞白血病及胃肠道间质瘤患者治疗药物伊马替尼血药浓度水平的影响,为临床个体化用药提供循证依据。方法　检索PubMed、EMBASE、Web of Sciences、Scopus、中国知网和万方数据库,搜集伊马替尼药动学通路转运体的ABCB1 C1236T、G2677T/A、C3435T基因多态性与接受伊马替尼治疗患者血药浓度的相关性研究。按照纳入及排除标准进行文献筛选、数据提取工作,并进行Meta分析。结果　共纳入ABCB1基因多态性与伊马替尼血药浓度水平相关性研究7篇,合计873例患者。Meta分析结果显示,ABCB1 C1236T中T等位基因携带者与C等位基因携带者间伊马替尼的稳态血药浓度差异有统计学意义（WMD=97.44 ng/ml,P=0.03）,G2677T/A中突变纯合及杂合基因携带者与野生型基因携带者间伊马替尼血药浓度差异有统计学意义（WMD=318.27 ng/ml,P<0.01）,未显示C3435T基因多态性与伊马替尼血药浓度具有显著关联性（P>0.05）。结论　ABCB1 C1236T、G2677T/A突变基因与伊马替尼血液浓度升高有关。     

The relationship between the CYP19 alleles rs727479A/C,rs700518A/G,and rs700519C/T and pregnancy outcome after assisted reproductive technology in patients with polycystic ovary syndrome in a Chinese population: A population-based study

This study investigated the relationship between the CYP19 alleles, rs727479A/C, rs700518A/G, and rs700519C/T, and pregnancy outcome after assisted reproductive technology (ART) in patients with polycystic ovary syndrome (PCOS). Between January 2012 and September 2015, 293 PCOS patients undergoing ART were randomly selected for the study. According to pregnancy outcome after ART, the patients were assigned to pregnancy and non-pregnancy groups. CYP19 rs727479A/C, rs700518A/G and rs700519C/T genotypes were determined using the denaturing high-performance liquid chromatography (DHPLC) method. Haplotype frequencies of the CYP19 alleles rs727479A/C, rs700518A/G and rs700519C/T were estimated using the SHEsis platform. Logistic regression analysis was employed to analyze the factors influencing the pregnancy outcome after ART. The frequency of the AC + CC genotype of rs727479A/C was higher in the pregnancy group than in the non-pregnancy group. The frequency of the CT + TT genotype of rs700519A/G was also higher in the pregnancy group than in the non-pregnancy group. Haplotype analysis indicated that the AAC and AGT haplotypes both exhibited unfavorable influence on the pregnancy outcome after ART. The AAT and CGT haplotypes were favorable to the pregnancy outcome after ART. Logistic regression analysis suggested that the rs727479A/C AA genotype, the rs700519C/T CC genotype and body mass index (BMI) might exert unfavorable influence on the pregnancy outcome after ART for PCOS patients. These findings indicated that the CYP19 alleles rs727479A/C and rs700519C/T might be associated with the pregnancy outcome after ART in patients with PCOS.     

IRAK1 rs3027898 C/A polymorphism is associated with risk of rheumatoid arthritis

IRAK1 and miR-499 play an important role in the etiology of rheumatoid arthritis. Few studies to date have focused on the influence of the IRAK1 rs3027898 C/A and hsa-mir-499 rs3746444 T/C polymorphisms in the susceptibility of the Chinese population to rheumatoid arthritis. We hypothesized that these polymorphisms may contribute to rheumatoid arthritis susceptibility. We studied IRAK1 rs3027898 C/A and hsa-mir-499 rs3746444 T/C gene polymorphisms in 214 rheumatoid arthritis cases and 478 controls in a Chinese population. Genotyping was performed by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). When the IRAK1 rs3027898 CC homozygote genotype was used as the reference group, the AA genotype was associated with significantly increased risk of rheumatoid arthritis (odds ratio (OR) = 1.91, 95 % confidence interval (CI) = 1.12–3.26, p = 0.017). A significantly increased risk of RA associated with the IRAK1 rs3027898 AA genotype was more evident among females, younger patients, CRP negative patients and both anti-CCP positive and negative patients compared with the IRAK1 rs3027898 CC/CA genotypes. The hsa-mir-499 rs3746444 T/C single nucleotide polymorphism (SNP) was not significantly associated with the risk for rheumatoid arthritis. Our findings suggest that the functional SNP IRAK1 rs3027898 C/A variant allele is associated with the development of rheumatoid arthritis. However, the hsa-mir-499 rs3746444 T/C polymorphism may not be associated with susceptibility to rheumatoid arthritis.     

Risk factors of phlegm syndrome in metabolic syndrome:EXT2 gene rs11037909/rs1113132/rs3740878-T allele,BMI and TG

<正>Objective To investigate the effect of single nucleotide polymorphisms (SNPs) of EXT2 gene on the susceptibility of metabolic syndrome (MS) with phlegm syndrome.Methods From November 2013 to December2020,a total of 849 patients with MS who were treated in the Pre Treatment Center and Physical Examination Center of the Third People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine,and the Endocrine Department of Jinjiang Hospital of Traditional Chinese Medicine A...     

半胱氨酸蛋白酶抑制因子Cystatin C基因与中国人脑卒中的关系

目的本文通过多中心病例．对照研究，拟探讨Cystatin C基因启动子区多态性位点rs2897119（-177C／T）和rs6114208（-1704C／G）与中国人脑卒中和血浆中半胱氨酸水平的关系。方法采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析技术，检测脑卒中组520例（血栓性脑梗塞组211例，腔隙性脑梗塞组145例，脑出血组164例），和非脑卒中对照组630例Cystatin C基因多态性的分布。用高效液相色谱仪和荧光检测仪测定血浆总Hey水平。结果脑卒中组和对照组Cystatin C基因rs2897119和rs6114208多态性基因型频数分布符合Hardy-Weinber平衡。两组rs2897119和rs6114208多态性基因型和等位基因型分布差异无明显统计学意义。各亚型组与对照组的基因型和等位基因型相比差异也均无显著统计学意义。两组多态性基因型与相应血浆同型半胱氨酸的水平也无显著统计学意义。结论Cystatin C基因多肽位点rs2897119（-177C／T）和rs6114208（-1704C／G）与中国人脑卒中和血浆同型半胱氨酸的水平不存在关联关系。Cystatin C基因多肽位点rs2897119和rs6114208可能不是中国人脑卒中的遗传影响因素。     

CYP7A1 (−204 A>C; rs3808607 and −469 T>C; rs3824260) promoter polymorphisms and risk of gallbladder cancer in North Indian population

Cholesterol 7-α hydroxylase (CYP7A1), which is a rate-limiting enzyme for cholesterol catabolism and bile acid synthesis, may affect cholesterol homeostasis and result in gallstone formation that is a major risk factor for gallbladder cancer (GBC) pathogenesis. Genetic variations in CYP7A1 may influence its expression and thus may affect the risk of gallstone disease and GBC. We aimed to study the association of 2 promoter polymorphisms of CYP7A1 (−204 A>C [rs3808607] and −469 T>C [rs3824260]) in gallstone and GBC susceptibility in North Indian population. The study included 185 GBC patients, 195 symptomatic gallstone patients, and 200 healthy controls. Genotyping for both polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism method. Although the CC genotype of CYP7A1 −204 A>C was not significantly associated with gallstone disease (P = .083, odds ratio [OR] = 1.69, 95% confidence interval [CI] = 0.9-3.0), it was conferring higher risk for GBC (P = .018, OR = 2.05, 95% CI = 1.1-3.7). However, CYP7A1 −469 T>C was not associated with gallstone disease and GBC risk in our population. After subgroup stratifications on the basis of sex and gallstone status, CC genotype and variant allele of CYP7A1 −204 A>C imparted higher risk for GBC in women (P = .003, OR = 3.30, 95% CI = 1.5-7.2) and patients without gallstones (P = .045, OR = 1.91, 95% CI = 1.2-3.6). Haplotype analysis of the 2 polymorphisms showed that C,T (P = .045, OR = 1.84, 95% CI = 1.0-3.3) and C,C (P = .0001, OR = 3.10, 95% CI = 1.6-6.0) haplotypes had elevated risk of GBC predisposition. CYP7A1 −469 T>C is not associated with gallstone disease or GBC risk. Although CYP7A1 −204 A>C might play a modest role in gallstone susceptibility, it is an independent risk factor for GBC in North Indian population. Underlying mechanism for GBC susceptibility by CYP7A1 (−204 A>C and −469 T>C) haplotype appears to be independent of gallstone pathway and is believed to involve genotoxicity resulting from subnormal bile acid production.