IL-17A基因单核苷酸位点多态性与胃癌预后的相关性研究

探讨白介素17A基因多态性与胃癌预后的关系。129例研究对象纳入生存分析,分成死亡和存活两组,用基因测序的方法检测血液样本IL-17A基因SNP位点rs3748067、rs17880588基因型分布。rs3748067位点有3种基因型T/T、C/T、C/C,rs17880588位点有2种基因型A/G、G/G。比较存活组和死亡组之间的基因型分布频率和单点等位基因分布频率,发现rs3748067的基因型C/T在死亡组的分布频率较存活组高,基因型T/T和C/C在死亡组的分布频率低于存活组,两组之间分布频率差异有统计学意义(P0.05)。杂合型C/T基因型在存活组分布低于死亡组(OR=2.051,CI=0.016~1.420),该位点基因型杂合可能为胃癌预后的一种危险因素。rs17880588的两种基因型A/G、G/G在存活组和死亡组的分布频率差异无统计学意义(P0.05)。结论:IL-17A基因rs3748067位点SNP与胃癌预后可能有相关性。     

基质金属蛋白酶-9 基因单核苷酸多态性与肺结核病的相关性研究

目的:探讨基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)基因多态性(single nucleotide polymorphism,SNP)与肺结核的相关性。方法:对符合纳入及排除标准的肺结核病例组224例及健康对照组249例进行血样收集与临床资料采集。采用飞行时间质谱分析方法对MMP-9基因rs17576、rs2236416、rs3787268、rs3918254共4个多态性位点进行基因分型,数据统计分析采用SPSS20.0和Haplo View 4.0软件进行。结果:我们首次发现,在病例及对照组中,rs17576基因型频率分布存在统计学差异(X~2=7.822,P=0.020)。与对照组相比,病例组G等位基因频率显著高于对照组(X~2=7.335,P=0.007,OR=1.463,95%CI=1.110-1.927)。病例组rs17576基因型分布中,GG和AG基因型患者吸烟史显著高于AA基因型患者;GG和AG基因型患者卡介苗接种史显著低于AA基因型患者。连锁不平衡分析发现一个单倍型(rs17576-rs3918254)高度连锁(D'0.7;r~20.8)。在病例组及对照组中,G-C和A-C单倍型频率分布存在显著性差异,病例组中G-C单倍型频率显著高于对照组(P=0.022),对照组中A-C单倍型频率显著高于疾病组(P=0.024)。结论:MMP-9基因rs17576多态性位点可能与肺结核有关,携带有rs17576位点G等位基因的个体更易发生肺结核。携带G-C(rs17576-rs3918254)单倍型的个体更易患肺结核病,携带A-C(rs17576-rs3918254)单倍型的个体相对不易患肺结核病。     

SLC6A4基因多态性与海洛因依赖的关联性研究

目的:探讨5-羟色胺转运体基因(solute carrier family 6 member 4,SLC6A4)基因4个单核苷酸多态性(single nucleotide polymorphism,SNP)位点与海洛因依赖之间的关系。方法:严格按照诊断标准,选取无亲缘关系的海洛因依赖个体397例(病例组)及健康对照个体402例(对照组)提取基因组DNA,采用SNaPshot SNP分型技术对SLC6A4基因4个SNP位点(rs1042173,rs3813034,rs6354,rs7224199)进行基因分型,比较病例-对照组间各位点等位基因、基因型频率的差异。结果:病例组和对照组SLC6A4基因rs1042173和rs3813034位点的基因型和等位基因频率比较存在显著性差异(P0.05),rs1042173的C等位基因(P=0.031,OR=1.317,95%CI=1.026-1.691)及rs3813034的C等位基因(P=0.013,OR=1.375,95%CI=1.069-1.768)是海洛因依赖的危险因素。病例组TCC单倍型(rs7224199、rs3813034和rs1042173)的比例较对照组显著增高(P0.05)。结论:SLC6A4基因rs1042173和rs3813034多态性可能与海洛因成瘾有关,携带有rs1042173的C等位基因和rs3813034的C等位基因的个体及携带TCC单倍型的个体可能更容易对海洛因产生依赖。     

2型糖尿病易感基因SNP位点对生活方式干预降低血糖应答效果的修饰效应

近年来的研究发现,一些2型糖尿病(type 2 diabetes mellitus, T2DM)易感基因位点不仅与T2DM的发病风险有关,还会影响生活方式干预效果。为进一步探究T2DM易感基因单核苷酸多态性(singlenucleotide polymorphism,SNP)位点对生活方式干预降低高危人群血糖应答效果的修饰作用,本课题组在德清农村社区开展了生活方式干预试验(2017年6月～12月,对干预组的研究对象进行强化生活方式干预,对照组仅接受常规健康知识宣教),并对研究对象进行SNP基因分型。研究发现,对于rs9502570,干预组中的CC+CT基因型人群的空腹血糖降低值显著高于TT基因型(P=0.031);干预组中CC+CT基因型人群的糖化血红蛋白值降低值为0.03%,TT基因型人群的糖化血红蛋白值升高了0.27%(P=0.012);CC+CT和TT基因型干预组和对照组的空腹血糖和糖化血红蛋白前后差值差之间也有统计学差异(均为P0.001)。对于rs10811661,干预组中TT基因型人群的空腹血糖降低值显著高于CC+CT基因型(P=0.021);TT和CC+CT基因型干预组和对照组的空腹血糖前后差值差之间亦有统计学差异(P0.001)。上述研究结果表明,rs9502570、rs10811661两个位点会在一定程度上修饰高危人群对T2DM生活方式干预降低血糖的应答效果,为今后进一步研制糖尿病高危人群个体化干预措施提供了客观依据。     

LKB1基因多态性与2型糖尿病相关性研究

目的:探讨陕西汉族人群中LKB1基因位点rs741765(380CT)及rs6510599(459GA)单核苷酸多态性(SNPs)与2型糖尿病遗传易感性及相关临床代谢指标的关系。方法:采用等位基因特异性引物PCR(SASP-PCR)对2型糖尿病患者130例及健康对照组100例进行LKB1基因内含子6 rs741765(380CT)及内含子1 rs6510599(459GA)两个位点进行基因多态性筛查,并测序鉴定,分析其基因多态性位点与2型糖尿病临床代谢指标关系。结果:rs741765(380CT)基因突变情况:2型糖尿病患者TT基因型频率显著高于健康对照组(P=0.023);TT基因2型糖尿病组中糖化血红蛋白水平及低密度脂蛋白胆固醇水平在型中明显升高(P=0.030;P=0.002);健康对照组中,空腹血糖水平在TT基因型中明显升高(P=0.011)。rs6510599(459GA)基因突变情况:AA基因型频率在2型糖尿病组及健康对照组间无显著性差异(P0.05);该基因位点与临床指标亦无相关性(P0.05)。结论:陕西汉族人群中LKB1基因内含子6 rs741765(380CT)及内含子1 rs6510599(459GA)存在基因多态性。LKB1基因内含子6 rs741765(380CT)基因多态性与2型糖尿病的发病有相关性。LKB1基因内含子1 rs6510599(459GA)基因多态性与2型糖尿病的发病无相关性。     

BRCA1 基因启动子区SNPs 与散发性乳腺癌易感性的相关研究

目的:探讨BRCA1基因启动子区rs11655505、rs73625095位点单核苷酸多态性与散发性乳腺癌易感性的关系。方法:采用ASA-PCR方法对200例乳腺癌患者(均经病理确诊)及200例正常女性BRCA1基因启动子区rs11655505(A/G)、rs73625095(A/G)位点单核苷酸多态性(SNP)进行分析,并将其PCR产物进行测序。结果:乳腺癌患者BRCA1基因启动子区rs11655505位点的A/G基因型频率为75%,显著高于正常人的40%;A/A基因型频率为7%,G/G基因型频率为18%,分别低于正常人的30%、30%。此位点的A或G等位基因在乳腺癌病例组及对照组中均无差别(x2=2.427,P=0.119);rs73625095位点的A/G基因型频率为68%,显著高于正常人的15%;G/G基因型频率为32%,低于正常人的84%;乳腺癌病例组中BRCA1基因启动子区rs11655505、rs73625095位点的A/G基因型与淋巴结转移与否相比,差别均有统计学意义(x2=7.321,P=0.026、x2=4.782,P=0.029)。结论:BRCA1基因rs11655505位点、rs736...     

apelin基因rs2235306位点多态性与哮喘的相关性研究

目的:探讨apelin基因rs2235306位点多态性与哮喘的相关性。方法:以外周血全血DNA为模板,应用四引物扩增受阻突变体系PCR(Tetra-primer ARMS PCR,T-ARMS-PCR)方法对158例哮喘患者(AS)和79例健康个体(NC)apelin基因rs2235306位点基因型进行分析,同时进行肺功能检查(FEV1、FVC、FEV1/FVC)。结果:AS组和NC组apelin基因rs2235306位点等位基因T和C频率分布具有统计学意义(X2=6.906,P=0.009,OR=1.688,95%CI=1.140-2.497),AS组C等位基因频率显著高于健康对照组;AS组和NC组基因型分布具有统计学意义(X2=14.243,P=0.000,OR=3.894,95%CI=1.861-8.149),其中CC基因型患哮喘的风险较高,为TT+TC基因型的3.894倍。AS轻度组和AS中重度组基因型CC和TT+TC频率及等位基因T和C频率比较均无统计学意义。结论:apelin基因rs2235306位点多态性和哮喘的发病具有一定的相关性,C等位基因可能是哮喘的遗传易感基因,CC基因型携带者哮喘的患病风险可能增加,但与哮喘的严重程度无明显相关性。     

SLC2A9rs1014290位点基因多态性与北方汉族地区男性痛风发病的相关性研究

目的:探讨可溶性载体2家族成员9基因(SLC2A9)rs1014290位点的单核苷酸多态性与北方汉族地区男性原发性痛风的发病的相关性。方法:选取404例原发性痛风男性患者和412名健康体检者,分别检测其血清尿酸、血脂、肾功等生化指标,同时提取外周血DNA,应用连接酶检测反应(LDR)法分析其SLC2A9基因rs1014290位点基因型和等位基因频率。结果:痛风组空腹血糖、尿酸(UA)、甘油三酯(TG)、胆固醇(TC)、收缩压、BMI、肌酐(Cr)水平均显著高于对照组,差异有统计学意义(P0.05)。痛风组SLC2A9基因rs1014290位点各基因型频率(CC:12.8%;CT:53.5%;TT:38.7%)与对照组(CC:16.2%;CT:50.9%;TT:32.9%)相比差异有统计学意义(X2=3.978,P=0.041);两组的等位基因频率相比差异无统计学意义(X2=0.314,P=0.496)。结论:SLC2A9基因rs1014290位点多态性可能与我国北方汉族男性原发性痛风的易感性相关,携带TT基因型的个体更易患痛风。     

口腔扁平苔藓患者的CIITA基因单倍型分析

目的:分析CIITA基因中单核苷酸多态性(Single Nucleotide Polymorphism,SNP)的单倍型与口腔扁平苔藓(Oral Lichen Planus,OLP)之间的关系,并探讨计算单倍型的新方法。方法:在得到42名患者与86名对照的CIITA基因中15个SNP位点的信息后,通过Haploview和SHEsis软件以及本研究组设计的频数计数法进行单倍型分析。组间比较使用χ2检验,并以P=0.05作为统计检验标准。结果:在本研究群体中,CIITA基因上的15个SNP位点能够形成两个单体域(haploblock),其中由位点rs6498124,rs11647384和rs4774所组成的单倍型GAC在三种单倍型分析方法中均显示出显著的统计学差异(Haploview:Chi2=6.127,P=0.013;SHEsis:Chi2=6.469 P=0.011;频数计数法:Chi2=5.460,P=0.019)。结论:在由CIITA基因的SNP位点rs6498124,rs11647384,rs4774组成的单体域中,单倍型GAC对OLP的患病具有潜在的保护性。频数计数法显示,rs4774位点本身的保护性及其与同一单体域内另外两个位点之间的完全连锁不平衡关系是单体型GAC显示出保护性的主要依据。提示单倍型对疾病易感性的解释在于其中的特定SNP位点等位基因型,及其该位点与其它相关位点间的连锁不平衡关系。     

BRCA1基因启动子区SNPs与散发性乳腺癌易感性的相关研究（英文）

目的：探讨BRCA1基因启动子区rs11655505、rs73625095位点单核苷酸多态性与散发性乳腺癌易感性的关系。方法：采用ASA-PCR方法对200例乳腺癌患者（均经病理确诊）及200例正常女性BRCA1基因启动子区rs11655505（A/G）、rs73625095（A/G）位点单核苷酸多态性（SNP）进行分析,并将其PCR产物进行测序。结果：乳腺癌患者BRCA1基因启动子区rs11655505位点的A/G基因型频率为75%,显著高于正常人的40%;A/A基因型频率为7%,G/G基因型频率为18%,分别低于正常人的30%、30%。此位点的A或G等位基因在乳腺癌病例组及对照组中均无差别（x2=2.427,P=0.119）;rs73625095位点的A/G基因型频率为68%,显著高于正常人的15%;G/G基因型频率为32%,低于正常人的84%;乳腺癌病例组中BRCA1基因启动子区rs11655505、rs73625095位点的A/G基因型与淋巴结转移与否相比,差别均有统计学意义（x2=7.321,P=0.026、x2=4.782,P=0.029）。结论：BRCA1基因rs11655505位点、rs73625095位点的A/G基因型可能与散发性乳腺癌的发生相关,而且与有无发生淋巴结转移密切相关。rs73625095位点A和G等位基因可能为散发性乳腺癌发生的遗传危险因素。     

Role of cytokine gene polymorphisms on prognosis in hepatocellular carcinoma after radical surgery resection

This study aimed to determine whether SNPs of cytokine genes influence survival of hepatocellular carcinoma (HCC) patients after radical surgery resection. We evaluated 14 SNPs of eight cytokine genes in 263 patients treated with radical surgery resection of HCC. Categorical variables were compared by the χ² test and Fisher's exact test. The Kaplan–Meier methods with log-rank test and Cox regression models were used to compare survival of resected HCC patients according to the genotype. Among the 14 studied SNPs of cytokine genes, only the TNF-α-863 (CA + CC) genotypes were revealed to be significant independent predictors of prolonged overall survival (OS) after HCC radical surgery resection (HR: 0.586, 95% CI: 0.355–0.968), considering for other clinical factors in a Cox proportional hazard model. Meanwhile, no significant association was found between the 14 SNPs and relapse-free survival (RFS) of resected HCC patients. In addition, combination analysis with the Th1 cytokine (IFN-γ, IL-2, IL-12B, TGF-β1) or Th2 cytokine (IL-6, IL-10) genetic polymorphisms by the Kaplan–Meier method and Cox multivariate analysis did not reveal any significant association between OS and RFS of resected HCC patients.     

Association between MCT1 T1470A polymorphism and climbing status in Polish and Japanese climbers

Sport climbing will become an official event at the 2020 Tokyo Olympics; it is a popular wilderness sport among athletes and amateurs. Our previous study suggested that the T1470A polymorphism (rs1049434) of the monocarboxylate transporter 1 (MCT1) gene is associated with athletic performance and physiological phenotypes. The purpose of this study was to investigate the frequency of MCT1 T1470A polymorphism in Polish and Japanese climbers using a case-control study. Our sample consisted of 226 climbers (Japanese: n = 100, 64 male and 36 female; Polish: n = 126, 97 male and 29 female) and 1028 non-athletic controls (Japanese, n = 407; Polish = 621) who were genotyped for the MCT1 T1470A polymorphism (rs1049434) using the TaqMan SNP genotyping assay or restriction enzyme. The frequency of the TT genotype and T allele was significantly higher in climbers than in controls among the Polish subjects (genotype: p = 0.030, allele: p = 0.010); however, there were no significant differences in the genotype and allelic frequencies between the Japanese climbers and controls (genotype: p = 0.968; allele: p = 0.803). Our results suggested that the frequency of the T allele (TT+TA genotype) in the MCT1 T1470A polymorphism is over-represented in Polish climbers but not in Japanese climbers. In addition, the frequency of the T allele and TT genotype in Polish lead climbers is higher than that in controls.     

Genetic Variants in the EPCAM Gene Is Associated with the Prognosis of Transarterial Chemoembolization Treated Hepatocellular Carcinoma with Portal Vein Tumor Thrombus

The epithelial cell adhesion molecule (EPCAM) is involved in the tumorigenesis and progression of many malignancies, including hepatocellular carcinoma (HCC). Single nucleotide polymorphisms (SNPs) of EPCAM have been reported to be with the risk and prognosis of several malignancies. However, the association of SNPs in EPCAM gene with the prognosis of HCC patients has never been investigated. In this study, two functional SNPs (rs1126497 and rs1421) in the EPCAM gene were selected and genotyped in a cohort of 448 unresectable Chinese HCC patients treated by TACE. The association of the two SNPs with the overall survival (OS) of patients was assessed by univariate and multivariate Cox proportional hazards model and Kaplan-Meier curve. Our data showed that there was no significant association between either SNP and OS of patients. However, in the stratified analysis, the variant-containing genotypes (WV+VV) of SNP rs1126497 exhibited a significant association with poorer OS in HCC patients who had portal vein tumor thrombus (PVTT) in multivariate analysis of Cox proportional hazard model (hazard ratio, 1.71; 95% confidence interval, 1.16–2.53, P = 0.007), and in Kaplan-Meier curve analysis (P = 0.023), comparing to those carrying wild-type genotype. Our results suggest that SNP rs1126497 in the EPCAM gene may serve as an independent prognosis biomarker for unresectable HCC patient with PVTT, which warranted further validating investigation.     

Host Genetics Predict Clinical Deterioration in HCV-Related Cirrhosis

Single nucleotide polymorphisms (SNPs) in the epidermal growth factor (EGF, rs4444903), patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409) genes, and near the interleukin-28B (IL28B, rs12979860) gene are linked to treatment response, fibrosis, and hepatocellular carcinoma (HCC) in chronic hepatitis C. Whether these SNPs independently or in combination predict clinical deterioration in hepatitis C virus (HCV)-related cirrhosis is unknown. We genotyped SNPs in EGF, PNPLA3, and IL28B from liver tissue from 169 patients with biopsy-proven HCV cirrhosis. We estimated risk of clinical deterioration, defined as development of ascites, encephalopathy, variceal hemorrhage, HCC, or liver-related death using Cox proportional hazards modeling. During a median follow-up of 6.6 years, 66 of 169 patients experienced clinical deterioration. EGF non-AA, PNPLA3 non-CC, and IL28B non-CC genotypes were each associated with increased risk of clinical deterioration in age, sex, and race-adjusted analysis. Only EGF non-AA genotype was independently associated with increased risk of clinical deterioration (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.31–6.25) after additionally adjusting for bilirubin, albumin, and platelets. Compared to subjects who had 0–1 unfavorable genotypes, the HR for clinical deterioration was 1.79 (95%CI 0.96–3.35) for 2 unfavorable genotypes and 4.03 (95%CI 2.13–7.62) for unfavorable genotypes for all three loci (P_trend<0.0001). In conclusion, among HCV cirrhotics, EGF non-AA genotype is independently associated with increased risk for clinical deterioration. Specific PNPLA3 and IL28B genotypes also appear to be associated with clinical deterioration. These SNPs have potential to identify patients with HCV-related cirrhosis who require more intensive monitoring for decompensation or future therapies preventing disease progression.     

Association study of four variants in <Emphasis Type="Italic">KCNQ1</Emphasis> with type 2 diabetes mellitus and premature coronary artery disease in a Chinese population

Four single nucleotide polymorphisms (SNPs, rs2237892, rs2237895, rs2237897, rs2283228) in KCNQ1 are associated with type 2 diabetes mellitus in different ancestral groups. We investigated whether these 4 genetic markers are determinants of type 2 diabetes and premature coronary artery disease (CAD) in a Chinese population. We studied 398 consecutive patients, including 180 with coronary stenosis ≥50% or previous myocardial infarction (male <55 years, female <65 years) and 218 controls without documented CAD. CAD cases and controls were genotyped for 4 SNPs by using the ligase detection reaction method. The 3 genotypes AA, AC, and CC were present in rs2283228 and rs2237895, and the 3 genotypes CC, CT, TT were present in rs2237897 and rs2237892. No differences were found in genotype distribution and allele frequencies of these 4 SNPs between subjects with and without type 2 diabetes. Logistic regression showed that the risk of premature CAD in subjects carrying the CC genotype at rs2237892 was reduced by 90% in relation to individuals carrying the TT genotype (OR = 0.100, 95% CI: 0.018–0.564, P = 0.009). The association of other 3 SNPs with premature CAD could not be detected, nor did there exist any association of these 4 SNPs among groups of patients with 0, 1, 2, and 3-vessel disease (all P > 0.05). Our data implicate rs2237892 in KCNQ1 as a protective gene variant against premature CAD and we couldn’t replicate any association of these 4 SNPs with T2DM or extent of coronary lesions in a Chinese population.     

Association between GWAS-Identified Genetic Variations and Disease Prognosis for Patients with Colorectal Cancer

Genome-wide association studies (GWASs) have already identified at least 22 common susceptibility loci associated with an increased risk of colorectal cancer (CRC). This study examined the relationship between these single nucleotide polymorphisms (SNPs) and the clinical outcomes of patients with colorectal cancer. Seven hundred seventy-six patients with surgically resected colorectal adenocarcinoma were enrolled in the present study. Twenty-two of the GWAS-identified SNPs were genotyped using a Sequenom MassARRAY. Among the 22 SNPs, two (rs1321311G>T in CDKN1A and rs10411210C>T in RHPN2) were significantly associated with the survival outcomes of CRC in a multivariate survival analysis. In a recessive model, the rs1321311 TT genotype (vs. GG + GT) and rs10411210 TT genotype (vs. CC + CT) were associated with a worse prognosis for disease-free survival (adjusted HR = 1.90; 95% confidence interval = 1.00-3.60; P = 0.050, adjusted HR = 1.94; 95% confidence interval = 1.05-3.57; P = 0.034, respectively) and overall survival (adjusted HR = 2.05; 95% confidence interval = 1.00-4.20; P = 0.049, adjusted HR = 2.06; 95% confidence interval = 1.05-4.05; P = 0.036, respectively). None of the other SNPs was significantly associated with any clinicopathologic features or survival. The present results suggest that the genetic variants of the CDKN1A (rs1321311) and RHPN2 (rs10411210) genes can be used as prognostic biomarkers for patients with surgically resected colorectal cancer.     

Combined effects of p53 and MDM2 polymorphisms on susceptibility and surgical prognosis in hepatitis B virus-related hepatocellular carcinoma

The p53 signaling pathway works as a potent barrier to tumor progression. Two single nucleotide polymorphisms (SNPs) in the gene loci of p53 pathway, p53 codon 72 Arg72Pro and MDM2 SNP309 (T>G), have been shown to cause perturbation of p53 function, but the effect of the two SNPs on the risk of hepatocellular carcinoma (HCC) remains inconsistent. This study investigated the influence of combined p53 Arg72Pro and MDM2 SNP309 on the risk of developing HCC in patients with chronic hepatitis B virus infection, and evaluated the significance of the two combined SNPs on patient prognosis. In total, 350 HCC patients, 230 non-HCC patients, and 96 healthy controls were genotyped for the p53 Arg72Pro and MDM2 SNP309. The combined p53 Pro/Pro and MDM2 G/G genotype was significantly associated with HCC risk (P= 0.047). Multivariate analysis indicated that combined p53 Pro/Pro and MDM2 G/G genotype was an independent factor affecting recurrence and survival (P<0.05). Patients with combined p53 Pro/Pro and MDM2 G/G genotypes had a poorer prognosis than other genotypes, P<0.01 for both disease-free survival (DFS) and overall survival (OS). DFS and OS rates also differed significantly between Barcelona Clinic Liver Cancer (BCLC) stage A patients with combined p53 Pro/Pro and MDM2 G/G and other genotypes (P<0.05). Thus, the combined p53 Pro/Pro and MDM2 G/G genotype is associated with increased risk of developing HCC and is an independent adverse prognostic indicator in early stage HCC.     

Genetic variation in IL28B is associated with the development of hepatitis B-related hepatocellular carcinoma

To evaluate the role of host IL28B (interleukin 28B; interferon lambda 3) single nucleotide polymorphisms (SNPs) in predicting hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) susceptibility, three SNPs in the IL28B gene (rs12979860C/T, rs8099917G/T and rs12980275G/A) were examined in 330 subjects (including 154 HBV-related HCC patients, 86 non-HCC patients with chronic hepatitis B (CHB), 43 HBV self-limited infections and 47 healthy controls). Notably, the frequency of CC homozygosity was 91.5% in healthy controls and 72.9% in CHB, the difference being statistically significant (χ(2) = 6.40, P = 0.01). The statistically difference was seen between healthy controls (91.5%) and HCC (74.7%) (χ(2) = 6.05, P = 0.01). However, this significant finding was not seen between HBV self-limited and healthy controls. Carriers of the minor T allele in rs12979860 had a higher risk of HCC compared with non-carriers (χ(2) = 4.44, P = 0.04). Haplotype analyses revealed significant association between haplotype C-T-A and healthy controls, but not with the HCC group (96.6 vs. 82.0%, χ(2) = 6.08, P = 0.01). Analyses of genotype combination and gene-gene interaction showed that there was a positive interaction between rs12979860 and rs12980275, with an OR rate of 11.79 (likelihood test, P = 0.04). Our results suggest that the IL28B rs12979860 C/T polymorphism might affect susceptibility to the chronic HBV infection and progression of HCC. Of note, the T allele and non-CC genotypes have strong predictive effect of increasing susceptibility of chronic HBV infection and HCC.     

Predictive value of ERCC1 single-nucleotide polymorphism in patients receiving platinum-based chemotherapy for locally-advanced and advanced non-small cell lung cancer--a pilot study

Platinum-based chemotherapy is the main type of I-line treatment of advanced and non-operative NSCLC patients without EGFR gene mutation. The excision repair cross-complementation group 1 (ERCC1) is an enzyme that executes the incision of the damaged DNA strand and removes platinum-induced DNA adducts. We investigated whether ERCC1 gene polymorphism has an effect on the response to chemotherapy and survival in 43 patients with NSCLC treated with platinum-based chemotherapy. ERCC1 19007 T>C SNPs were assessed using a PCR-RFLP methods in DNA isolated from peripheral blood lymphocytes. Disease control occurred significantly (p = 0.045) more frequently in patients with CC or CT genotype compared to patients with TT genotype. Median PFS and OS for CC homozygous were 4 and 10.5 months, 4 and 12.5 months for CT heterozygous, but only 0.3 and 1.5 months for TT homozygous patients, respectively. The probability of PFS was significantly higher (HR = 0.438, 95% CI: 0.084-0.881, p = 0.03) and probability of OS was insignificantlyhigher (HR = 0.503, 95% CI: 0.129-1.137, p = 0.084) in patients with CC or CT genotype than in patients with TT genotype. Uncommon TT genotype of ERCC1 19007 T>C polymorphism could predict poor response and shortening of progression free survival in NSCLC patients treated with platinum-based I-line chemotherapy. The analysis of this polymorphism may serve as a promising tool in the qualification of advanced NSCLC patients for appropriate chemotherapy.     

The role of FOXP3 rs3761548 and rs2294021 polymorphisms in pediatrics acute lymphoblastic leukemia: association with risk and response to therapy

FOXP3 X-linked gene has crucial roles in the development and function of regulatory T cells. We investigated the association of FOXP3 rs3761548, rs3761549 and rs2294021 single nucleotide polymorphisms (SNPs) with acute lymphoblastic leukemia (ALL) susceptibility and response to therapy. Genotyping was performed in 247 patients and 210 healthy subjects. We observed a higher frequency of rs3761548 A carriers and rs2294021 C carriers (p?<?0.04) in male patients, and lower frequencies of rs3761548 AC genotype (p?=?0.04) and rs2294021 CT genotype (p?=?0.01) in female patients compared to controls. ACC (p?=?0.04) and ATC haplotypes (p?=?0.002) were associated with susceptibility to ALL. There was a significant correlation between the genotypes of rs3761548 and rs2294021 SNPs with event-free survival (EFS) and overall survival (OS). The rs3761548 A genotype in male patients was associated with increased risk of relapse (p?<?0.0001), shorter EFS, increased death rate (p?=?0.002) and shorter OS compared to C genotype (p?=?0.001). Similar significant results were observed for the relation of rs2294021 C genotype with response to therapy in male patients. In females, patients with rs3761548 AC genotype had longer EFS (p?=?0.02) and those with rs2294021 CT had longer EFS and OS (p?<?0.005). According to haplotype analysis, patients carrying ACC or ATC haplotypes had the highest number of WBCs and shorter EFS or OS, and patients with CCT haplotype had the lowest number of WBCs and longer EFS or OS. These results provided evidence for the impact of these polymorphisms on susceptibility and response to therapy in children with ALL.