汉民族XRCC1基因399位密码子单核苷酸多态性与原发肝癌关系的研究

目的探讨汉民族XRCC1基因399位密码子单核苷酸多态性与原发肝癌之间的关系。方法原发肝癌患者50例,肝炎肝硬化患者61例,健康献血人员92例。针对XRCC1基因的10号外显子设计引物,PCR产物利用MspⅠ限制性酶切进行基因分型,基因型分成XRCC1 399Arg/Arg,399Arg/Gln,399Gln/Gln三种,分析XRCC1多态性与肝癌之间的关系。结果原发肝癌患者中XRCC1 399Arg/Arg 32例(64.0%),Arg/Gln 14例(28.0%),Gln/Gln 4例(8.0%);肝炎肝硬化患者中Arg/Arg 30例(49.2%),Arg/Gln 23例(37.7%),Gln/Gln 8例(13.1%);健康人群Arg/Arg 46例(50.0%),Arg/Gln 41例(44.5%),Gln/Gln 5例(5.5%)。以健康人群为对照组,XRCC1399Gln基因(基因型Arg/Gln和Gln/Gln)并不增加患肝癌的风险性(OR=0.563,95%CI:0.277-1.141,P=0.109);以肝炎肝硬化为对照组,XRCC1 399Gln基因同样与患肝癌的易感性之间没有显著的相关性(OR=0.544,95%CI:0.253-1.170,P=0.118)。结论XRCC1基因密码子399位点的基因多态性与汉民族原发肝癌危险性无统计学相关关系。     

中国人群XRCC1 Arg399Gln基因多态性与肝癌易感性Meta分析

目的:系统评价中国人群X线修复交叉互补基因1(X-ray repair cross complementing group 1,XRCC1)Arg399Gln基因多态性与肝癌易感性的关系.方法:在Pub Med、MEDLINE、EMBASE、CNKI、CBM、VIP及万方数据库中检索2000-01-01/2015-01-10发表的所有有关中国人群XRCC1 Arg399Gln基因多态性与肝癌易感性关系的相关文献.按照纳入和排除标准独立选择文献、提取资料,采用Stata12.0软件进行Meta分析,计算合并比值比(odds ratio,OR)及其95%可信区间(95%confidence interval,95%CI),并进行敏感性分析和发表偏倚的估计.结果:按照入选标准,共纳入13个研究,包括2972例患者和3789例对照者.Meta分析结果显示,与基因型Arg/Arg、Arg/Arg+Arg/Gln分别进行比较,基因型Gln/Gln均增加中国人群罹患肝癌风险(OR=1.47,95%CI:1.24-1.74,P0.001;O R=1.26,95%C I:1.08-1.48,P=0.003);与基因型Arg/Arg进行比较,基因型Gln/Gln+Arg/Gln增加中国人群罹患肝癌风险(OR=1.49,95%CI:1.21-1.83,P0.001).与等位基因Argalele比较,等位基因Gln-allele增加中国人群罹患肝癌的风险(OR=1.33,95%CI:1.16-1.54P0.001).结论:XRCC1 Arg399Gln基因多态性与中国人群肝癌易感性相关,基因型Gln/Gln增加中国人群罹患肝癌的风险.     

XRCC1基因(Arg399Gln)多态性与肝细胞癌易感性关系的Meta分析

目的探讨XRCC1基因(Arg399Gln)多态性与肝细胞癌易感性的关系。方法通过万方、CNKI、Medline、Pub Med、CMB、VIP等公开发表的国内外数据库进行检索,制定检索式对XRCC1基因(Arg399Gln)与肝细胞癌易感性之间关系的研究进行检索。收集2011年至2018年发表的全部相关文献,根据确定的准入标准对文献进行初筛、质量评价、数据提取,同时兼顾文献的权威性、时效性等方面,并通过Rev Man 5. 3软件进行分析。结果最终纳入符合要求文献共9篇,均为病例-对照研究,共计6 671例。其中病例组为3 094例,对照组为3 577例。XRCC1基因表现为AA、A/G、GG型,分别以A为显性基因及A为隐性基因进行对比。分析显示显性基因模型差异无统计学意义(OR=0. 72,95%CI:0. 46～1. 12,P=0. 14),隐性基因模型差异有统计学意义(OR=1. 36,95%CI:1. 01～1. 84,P=0. 04)。结论 A为显性基因模型时XRCC1基因(Arg399Gln)多态性对肝细胞癌的发生、发展无任何作用,A为隐性基因模型时XRCC1基因(Arg399Gln)多态性对肝细胞癌的发生、发展具有促进作用。     

XRCC1和XPD单核苷酸多态性与非小细胞肺癌铂类药物化疗敏感性的关系

目的研究X线修复交叉互补基因1（XRCC1）和着色性干皮病基因（XPD）单核苷酸多态性与老年晚期非小细胞肺癌（NSCLC）铂类药物化疗敏感性关系。方法应用聚合酶链反应结舍限制性片段长度多态性（PCR-RFLP）的方法检测81例以铂类药物为主要化疗方案的NSCLC患者XRCC1 Arg399Gln和XPD Lys751Gin基因型多态性，采用非条件Logistic回归分析不同基因型与化疗疗效的关系。结果81例患者化疗总有效率为35．8％，其中完全缓解（CR）、部分缓解（PR）、稳定（SD）和进展（PD）患者分别为0、29、31、21例。携带至少1个XRCC1 399Arg等位基因的患者化疗敏感性是携带Gln／Gln基因型患者的4.52倍（OR=4．52，95％CI=1.11—18．38）。未发现XPD Lys751Gin遗传多态与化疗敏感性相关。结论XRCC1 Arg399Gln多态可能与晚期NSCLC铂类药物化疗敏感性有关。     

晚期NSCLC患者放疗效果与XRCC1 SNP的关系

目的评价晚期非小细胞肺癌(NSCLC)患者放射性治疗疗效及副作用与XRCC1 Codon399单核苷酸多态性的相关性。方法经皮肺穿刺活检病理确诊为鳞癌、腺癌、腺鳞癌或大细胞癌患者60例,以xTAG液相芯片技术检测XRCC1 Codon399的3种基因型。随访至放疗结束后3个月,评价放疗效果和放射性损伤与不同基因型的关系。结果各组在放疗效果方面未发现显著差异。Arg/Gln杂合子组患者发生急性放射性肺损伤的比例高于两组纯合子(P0.05),Arg/Gln和Gln/Gln组患者在消化道损伤方面要高于Arg/Arg纯合子组(P0.05)。在皮肤、食管损伤以及白细胞、血小板等指标未发现显著差异(P0.05)。结论XRCC1 Codon399单核苷酸多态性与NSCLC放疗敏感性无关,但与晚期NSCLC患者肺部及消化道的急性放射性损伤有关,有望成为放射治疗副作用的预测因子之一。     

DNA修复基因XRCC1 Arg194Trp Arg280His和Arg399Gln多态性与前列腺癌相关性的Meta分析

目的探讨DNA修复基因X线修复交叉互补因子1（XRCC1）主要单核苷酸多态性与前列腺癌易感性的关系。方法在MEDLINE、EMBASE和OVID数据库上检索文献,收集及提取符合纳入标准的以XRCC1密码子194、280、399多态性与前列腺癌易感性为内容的病例对照研究文献,应用Stata统计软件进行Meta分析,比值比（ORs）及其95%可信区间（95%CI）评价关联强度;应用SPSS软件分析吸烟与前列腺癌关系,OR？评价其相对危险度。结果 XRCC1 399 Gln/Gln和XRCC1 280 Arg/His与前列腺癌的发病风险有关（Gln/Gln vs Arg/Arg：OR？=1.27,95%CI=1.02～1.59;Arg/His vs Arg/Arg：OR？=1.66,95%CI=1.09～2.52）,尤其在亚组分析中亚洲人的Gln/Gln明显增加了前列腺癌的发病风险（OR？=1.52,95%CI=1.18～1.96）;Arg194Trp与前列腺癌的发病风险无明显关联。吸烟是前列腺癌的危险因素（χ2=13.974,P=0.000,OR？=1.22）。结论 XRCC1 399 Gln/Gln和280 Arg/His可能与前列腺癌的易感性相关。     

X线损伤交叉互补基因1多态性与结直肠癌易感性研究

目的 探讨DNA修复酶X线损伤交叉互补基因1(XRCC1 )外显子三个位点的基因多态性(Arg194Trp 、Arg280His、Arg399Gln)与结直肠癌(CRC)发病风险的关系.方法 以聚合酶链反应和限制性片段长度多态性(PCR-RFLP)分析方法,采用病例-对照研究,对250例CRC患者(病例组,其中结肠癌128例,直肠癌122例)和213名健康人(对照组)的XRCC1基因三个位点的多态性进行了检测,采用SPSS 11.0软件包统计分析各位点的基因型分布和等位基因频率.结果 XRCC1基因194和399二个位点的各基因型频率在两组间分布差异均无统计学意义(P值均>0.05),但病例组XRCC1基因280 Arg/His基因型频率较对照组显著增高(校正后OR=1.66,95%CI:1.01～2.73,P=0.047).在直肠癌患者组中,280Arg/His基因型频率较对照组显著增高(OR=1.82,95%CI:1.02～3.27),携等位基因280His(Arg280His +His280His)的CRC患者的频率显著高于其在对照组中的频率(校正后OR=1.85,95%CI:1.06～3.22),而在结肠癌患者中风险系数相对较低且差异无统计学意义(校正后OR=1.31,95%CI:0.74～2.35).结论 XRCC1 Arg194Trp和 Arg399Gln基因多态性与结肠癌易感性无关,但280Arg/His基因型能增加CRC易感性,等位基因280His是直肠癌风险因素.

Abstract：

Objective To investigate the correlation between three gene locus polymorphisms of X-ray repair cross-complementary protein 1 (XRCC1) exon (Arg194Trp, Arg280His and Arg399Gln) and the risk of colorectal cancer (CRC). Methods A case-control study was performed in 250 CRC patients (case group, 128 colon cancer patients and 122 rectal cancer patients) and 213 healthy individuals (control group). The three gene locus polymorphism of XRCC1 was tested by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The genotype distribution and allele frequency of each locus was analyzed with SPSS 10.0 software. Results There was no significant difference in allele frequency of XRCC1 at 194 and 399 loci (P > 0.05). However, the 280 Arg/His allele frequency of XRCC1 was higher in case group than that in control group (OR=1.66,95%CI:1.01~2.73,P=0.047). The 280Arg/His allele frequency was higher in rectal cancer group than that in control group (OR =1.82,95%CI:1.02~3.27). The frequency of 280His allele (Arg280His and His280His) was higher in case group than that in control group (OR=1.85,95%CI:1.06~3.22). However, it was a relative low risk factor of colon cancer and there was no significant difference between colon cancer group and control group (OR=1.85, 95%CI:1.06~3.22). Conclusions There was no correlation between XRCC1 Arg194Trp and Arg399Gln polymorpohisms and the risk of CRC. However, 280Arg/His genotype may increase the risk of CRC, and 280His allele is a risk factor of rectal cancer.     

对氧磷酶1基因Gln192Arg多态性与阿尔茨海默病的相关性分析

目的 探讨中国汉族人群中对氧磷酶1（PON1）基因Gln192Arg单核苷酸多态性（SNP）与阿尔茨海默病（AD）的相互关系。方法采用实时定量PCR技术检测521例AD患者和578例健康老年人PON1基因Gln192Arg位点SN-P的分布,并通过OR做疾病关联分析。结果AD组（Q／R＋R／R）基因型频率较对照组低,统计分析差异有统计学意义（X^2=4．68,P=0．03）;等位基因频率差异也存在统计学意义,AD组R等位基因频率明显低于对照组（X^2=3．85,P=o．05）。logistic回归分析表明,调整年龄和性别的影响后,（Q／R＋R／R）基因型患AD的危险性是Q／Q基因型的0．71倍（P=0．044,95％CI=0．51～0．99）。结论中国汉族人群中PON1基因Gln192Arg位点R等位基因可能是AD的保护因素。     

慢性HBV感染者外周血单个核细胞CTLA-4基因多态性与病情转归的关联研究

目的初步探讨慢性HBV感染者外周血细胞毒性T淋巴细胞相关抗原-4（CTLA-4）基因第1外显子区49位基因单核苷酸多态性（single nucleotide polymorphism，SNP）与乙型肝炎病毒感染转归的关系。方法采用聚合酶链式反应-限制性片段长度多态性法检测190例慢性HBV感染者和93例既往HBV感染者外周血CTLA-4基因49位点的多态性。结果慢性HBV感染者CTLA-4基因49位点A／G基因型分布与对照组比较差异有显著性（P=0．034），慢性感染者G等位基因频率明显低于对照组（0．561对0．677，P=0．008，OR=0．607）。结论CTLA-4第1外显子49位基因多态性可能与乙型肝炎病毒感染慢性化相关。     

DNA损伤修复基因hOGG1的遗传多态与乙肝相关性HCC的风险

目的:探讨DNA损伤修复基因hOGGI的遗传多态Ser326Cys与肝细胞癌(HCC)易感性的关系．方法:应用基因测序分型方法,分析96例HCC患者和96例健康对照hOGG1的遗传多态及与HBV感染的交互作用．结果:HCC病例组的Cys／Cys,Cys／Ser和Ser／Ser基因型分别为20．9％,44．2％和34．9％．Ser／Cys杂合子个体的OR值为1．5,Cys／Cys纯合子个体的OR值为1．9,明显高于Ser/Ser个体,表现出剂量效应．HBV感染者发生HCC的相对风险度是非HBV感染者的9倍(OR=9．2;95％CI 0．99-5．9)．对于HCC,hOGG1-Ser326Cys变异或HBV感染单一因素的OR值分别为5．5 (95％CI 0．7-240．1)和10．9(95％CI1．6-453．3),但携带变异基因者如果感染HB V,OR值则高达27．8(95％CI4．7-970．2)．结论:DNA修复基因hOGG1的Cys等位基因可能增加HCC的遗传易感性,他与HBV协同在乙肝相关性HCC的发生中起着重要作用．     

XRCC1 genetic polymorphism Arg399Gln and hepatocellular carcinoma risk: a meta‐analysis

Background: Studies investigating the association between X‐ray repair cross‐complementing group 1 (XRCC1) genetic polymorphism Arg399Gln and hepatocellular carcinoma (HCC) risk report conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship. Methods: Two investigators independently searched the Medline, Embase, CNKI and Chinese Biomedicine Database. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for XRCC1 polymorphism and HCC were calculated in a fixed‐effects model (the Mantel–Haenszel method) and a random‐effects model (the DerSimonian and Laird method) when appropriate. The pooled ORs were performed for a codominant model (Gln/Gln vs. Arg/Arg, Arg/Gln vs. Arg/Arg), a dominant model (Gln/Gln+Arg/Gln vs. Arg/Arg) and a recessive model (Gln/Gln vs. Arg/Gln+Arg/Arg). Results: This meta‐analysis included 11 case–control studies, which included 2208 HCC cases and 3265 controls. Overall, the variant genotypes (Gln/Gln and Arg/Gln) of Arg399Gln were not associated with HCC risk when compared with the wild‐type Arg/Arg homozygote (Gln/Gln vs. Arg/Arg, OR=1.01, 95% CI=0.79–1.28; Arg/Gln vs. Arg/Arg, OR=1.09, 95% CI=0.81–1.45). Similarly, no associations were found in the dominant and recessive models (dominant model, OR=1.12, 95% CI=0.85–1.47; recessive model, OR=0.99, 95% CI=0.79–1.25). Limiting the analysis to the studies within Hardy–Weinberg equilibrium, the results were persistent and robust. When stratifying for ethnicity, country/region and source of controls, no evidence of a significant association was observed in any subgroup. No publication bias was found in the present study. Conclusion: No association is found between the XRCC1 polymorphism Arg399Gln and the risk of HCC.     

X-ray repair cross-complementing group 1 polymorphisms and hepatocellular carcinoma: a meta-analysis

AIM: To perform a systematic meta-analysis to investigate the association between X-ray repair cross-complementing group 1 (XRCC1) polymorphisms and hepatocellular carcinoma (HCC) risk.METHODS: Relevant studies extracted from PubMed, Embase, Wanfang, VIP and the Chinese National Knowledge Infrastructure databases up to March 2012 were included in the study. Stata software, version 11.0, was used for the statistical analysis. The odds ratios (ORs) and 95% confidence interval (CI) of the XRCC1 polymorphisms in HCC patients were analyzed and compared with healthy controls. The meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity.RESULTS: Eleven studies with 2075 HCC cases and 2604 controls met our eligibility criteria (four studies, 888 cases and 938 controls for Arg194Trp, four studies, 858 cases and 880 controls for Arg280His, and nine studies, 1845 cases and 2401 controls for Arg399Gln). The meta-analysis revealed no associations between the Arg194Trp and Arg399Gln polymorphisms of the XRCC1 gene and HCC risk under all contrast models (codominant, dominant and recessive models) in the overall analysis and sensitivity analysis (the studies with controls not in the Hardy-Weinberg equilibrium were excluded). For XRCC1 Arg280His polymorphism, the overall analysis revealed the significant association between the His/His genotype and the increased risk of HCC (His/His vs Arg/Arg model, OR: 1.96, 95% CI: 1.03-3.75, P = 0.04). However, sensitivity analysis showed an altered pattern of result and non-significant association (OR: 2.06, 95% CI: 0.67-6.25, P = 0.20). The heterogeneity hypothesis test did not reveal any heterogeneity, and Begg’s and Egger’s tests did not find any obvious publication bias.CONCLUSION: The XRCC1 Arg194Trp and Arg399Gln polymorphisms are not associated with HCC risk. More rigorous association studies are needed to verify the involvement of XRCC1 Arg280His polymorphism in HCC susceptibility.     

Polymorphisms of XRCC1 gene and risk of gastric cardiac adenocarcinoma

X-ray repair cross complementing 1 (XRCC1) protein plays an important role in base excision repair. Single nucleotide polymorphisms (SNPs) in XRCC1 gene may affect DNA repairing ability and genetic susceptibility to cancer. This study was designed to investigate the correlation of XRCC1 Arg194Trp Arg280His and Arg399Gln SNPs with the risk of gastric cardiac adenocarcinoma (GCA). Genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay in 455 patients with GCA and 650 age- and sex-matched controls. We did not find any significant difference in allele and genotype distributions of Arg194Trp Arg399Gln between the groups ( P  > 0.05). However, a significant increase in GCA risk was seen among smokers if they carried at least one XRCC1 280His ( Arg280His  +  His280His ) genotype (odds ratio = 1.59, 95% confidence interval = 1.01–2.51) compared with smokers not carrying these genotype. Our results indicated that XRCC1 Arg194Trp and Arg 399 Gln SNPs might not be associated with the risk of GCA. However, smokers with His allele at codon 280 had a significantly increased risk of GCA.     

Rheumatoid arthritis risk associates with DNA repair gene XRCC1 Arg399Gln polymorphism in Turkish patients

Rheumatoid arthritis (RA) is an autoinflammatory disease with a genetic background. The synoviocytes in RA shows cellular transformation with tumor-like features, and RA patients have genomic instability and relaxation of DNA repair mechanisms. The polymorphisms in BER repair pathway genes, XRCC1 and OGG1, may change the response to inflammation via altered DNA repair capacity. In this study, we aimed to investigate the relationship between the risk of RA and XRCC1 Arg194Trp, Arg399Gln, and OGG1 Ser326Cys polymorphisms in a group of Turkish RA patients. XRCC1 Arg194Trp, Arg399Gln, and OGG1 Ser326Cys polymorphisms were investigated by PCR–RFLP method in 100 RA patients and 158 healthy control subjects. The results were statistically analyzed by calculating the odds ratios (OR) and their 95% confidence intervals (95% CI) using the χ²-tests. RA patients in this study had significantly higher frequencies of XRCC1 Arg399Gln polymorphism in both homozygote (GG) (35%, OR: 7.78 [95% CI: 3.65–16.59], P < 0.001) and heterozygote (AG) forms (41%, OR: 2.17 [95% CI: 1.19–3.96], P < 0.01) and also increased frequency of 399Gln (G) allele (55%, OR:2.99 [95% CI: 1.67–5.37], P < 0.001). We conclude that XRCC1 Arg194Trp, and OGG1 Ser326Cys polymorphisms are not associated with RA; however, Arg399Gln polymorphism is a significant risk factor of RA, and carriers of 399Gln (G) allele have greater risk of RA.     

XRCC1 Arg399Gln, Arg194Trp, and Arg280His Polymorphisms in Esophageal Cancer Risk: A Meta-Analysis

Background

The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair.

Aim

To elucidate the role of XRCC1 Arg399Gln, Arg194Trp and Arg280His genotypes in esophageal cancer risk, all available studies were considered in the present meta-analysis.

Methods

Eligible studies were identified by searching several electronic databases for relevant reports published before June 2012.

Results

According to the inclusion criteria and exclusion criteria, a total of 21 eligible studies were included in the pooled analyses. Among the 21 studies, 18 focused on Arg399Gln polymorphism, 11 described the Arg194Trp, and 4 articles investigated on Arg280His. Our analysis suggested that there was no evidence of significant association between XRCC1 Arg399Gln polymorphism and esophageal cancer risk in any genetic model. In the stratified analysis by ethnicity for Arg399Gln polymorphism and esophageal cancer, the results showed that Arg399Gln polymorphism was not associated with esophageal cancer risk. Only 4 studies analyzed the relationship between XRCC1 Arg280His polymorphism and the risk of esophageal cancer. The Arg/His and His/His genotypes were not significantly associated with increased risk of EC. A similar negative association was maintained in dominant and recessive models. However, for XRCC1 Arg194Trp polymorphism, our study showed individuals carrying the variant genotype Trp/Trp had a significant increased risk of esophageal cancer (OR = 1.295, 95 % CI 1.053–1.591, P = 0.014). In addition, increased associations were found in recessive model (OR = 1.332, 95 % CI 1.093–1.624, P = 0.005).

Conclusions

Our meta-analysis suggested that Arg194Trp Trp allele might act as a risk allele in its association with esophageal cancer.     

The association between RAD18 Arg302Gln polymorphism and the risk of human non-small-cell lung cancer

Purpose The repair enzyme RAD18 plays a key role in the post-replication repair process in various organisms from yeast to human, and the molecular function of the RAD18 protein has been elucidated. Single nucleotide polymorphism (SNP) of arginine (Arg, CGA) or glutamine (Gln, CAA) at codon 302 is known on RAD18; however, the association between the SNP and the risk of any human cancers including non-small-cell lung cancer (NSCLC) has not been reported. We therefore investigated the relationship between the polymorphism and the development and progression of human NSCLC. Methods The study population included 159 patients with NSCLC and 200 healthy controls. The SNP was genotyped by polymerase chain reaction with the confronting two-pair primer (PCR-CTPP) assay. Genotype frequencies were compared between patients and controls, and the association of genotypes with clinicopathological parameters was also studied. Results The Gln/Gln genotype was significantly more frequent in NSCLC patients (20.7%) than in healthy controls (11.5%)(P = 0.003). The increased risk was detected in NSCLC patients with the Gln/Gln genotype [Odds ratio (OR) = 2.63, 95% confidence interval (CI)=1.38–4.98]. As to the relationship of the SNP with clinicopathological parameters of NSCLC, significantly higher risks were detected in lung squamous cell carcinoma (LSC) (OR = 4.40, 95% CI = 1.60–12.1). Conclusions Our results suggested that Gln/Gln genotype of the RAD18 SNP has the increased risk of NSCLC, especially of LSC. This is the first report to provide evidence for an association between the RAD18 Arg302Gln polymorphism and human NSCLC risk.     

Adenosine diphosphate ribosyl transferase and x-ray repair cross-complementing 1 polymorphisms in gastric cardia cancer

BACKGROUND & AIMS: Adenosine diphosphate ribosyl transferase (ADPRT) and x-ray repair cross-complementing 1 (XRCC1) are major DNA base excision repair proteins acting interactively in repair processes. This study examined the effects of ADPRT Val762Ala and XRCC1 Arg399Gln polymorphisms on ADPRT-XRCC1 interaction in vitro in cells and their contributions to gastric cardia adenocarcinoma (GCA) risk. METHODS: The ADPRT-XRCC1 interaction in cells transfected with ADPRT and XRCC1 variant complementary DNA (cDNA) constructs were examined by immunoprecipitation and immunoblotting analysis. Genotypes were analyzed in 500 patients and 1000 controls, and odds ratios (ORs) were estimated by logistic regression. RESULTS: Interactions between ADPRT-762Val and XRCC1-399Arg or XRCC1-399Gln were robust, but interactions between ADPRT-762Ala and either XRCC1-399Arg or XRCC1-399Gln were very weak. A case-control analysis showed ORs of 2.17 (95% CI, 1.55-3.04) and 1.61 (95% CI, 1.06-2.44) for GCA in the ADPRT Ala/Ala or XRCC1 Gln/Gln genotype carriers, respectively, compared with noncarriers. Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased the OR of GCA in a multiplicative manner (OR for the presence of both ADPRT Ala/Ala and XRCC1 Gln/Gln genotypes, 6.43; 95% CI, 1.80-22.97). A supermultiplicative joint effect between the ADPRT polymorphism and smoking was observed. The ORs (95% CIs) of the Ala/Ala genotype for nonsmokers and smokers who smoked < or = 24 or > 24 pack-years were 1.44 (0.89-2.32), 2.00 (1.09-3.67), or 3.19 (1.59-6.42), respectively (Ptrend test = .008). CONCLUSIONS: The ADPRT and XRCC1 polymorphisms confer host susceptibility to GCA, which might result from reduced ADPRT-XRCC1 interaction and attenuated base excision repair capacity.     

Homozygosity for Pro of p53 Arg72Pro as a potential risk factor for hepatocellular carcinoma in Chinese population

AIM: Codon 72 exon 4 polymorphism (Arg72Pro) of the p53 gene has been implicated in cancer risk. Our objective was to investigate the possible association between p53 Arg72Pro polymorphism and susceptibility to hepatocellular carcinoma (HCC) among Chinese population, METHODS: The p53 Arg72Pro genotypes were determined by PCR-based restriction fragment length polymorphism (RFLP) analysis in 507 HCC cases and 541 controls. Odds ratios (ORs) for HCC and 95% confidence intervals (CIs) from unconditional logistic regression models were used to evaluate relative risks. Potential risk factors were included in the logistic regression models as covariates in the multivariate analyses on genotype and HCC. RESULTS: The frequencies for Pro and Arg alleles were 44.5%, 55.5% in HCC cases, and 40.3% and 59.7% in controls, respectively. The Pro allele was significantly associated with the presence of HCC (P = 0.05) and had a higher risk for HCC (OR = 1.19, 95% CI 1.00-1.41) as compared with the Arg allele. After adjusted for potential risk factors, Arg/Pro heterozygotes had an 1.21-fold increased risk (95% CI 0.82-1.78, P= 0.34) of HCC compared with Arg homozygotes, whereas the risk for Pro homozygotes was 1.79 (95% CI 1.06-3.01, P= 0.03) times higher than that for Arg homozygotes. Pro-allele carriers had a higher relative risk of HCC than the Arg-only carriers (adjusted OR = 1.33, 95% CI 0.92-1.92, P = 0.13), although the difference was not statistically significant. CONCLUSION: Homozygosity for Pro of p53 Arg72Pro is potentially one of the genetic risk factors for HCC in Chinese population. The p53 Arg72Pro polymorphism may be used as a stratification marker in screening individuals at a high risk of HCC.     

Paraoxonase 1 Gln/Arg polymorphism is associated with the risk of microangiopathy in Type 2 diabetes mellitus.

AIMS: To investigate possible associations between diabetic microangiopathy and genetic polymorphisms in factors relevant to arterial thrombosis. METHODS: We conducted a case-control study on a total of 280 patients with Type 2 diabetes, comparing those without retinopathy or nephropathy (n = 92) and those with microangiopathies (n = 188), for the association of polymorphisms in four candidate genes, paraoxonase 1 (PON1), plasminogen activator inhibitor-1, fibrinogen, and platelet glycoprotein Ibalpha. RESULTS: There were no differences between the two study groups in gender distribution, age at diagnosis of diabetes (47.9 +/- 8.4 and 49.0 +/- 11.4 years, respectively), or duration of diabetes (14.9 +/- 4.5 and 14.5 +/- 8.4 years, respectively). Among the gene polymorphisms tested, the 192Gln/Arg polymorphism of PON1 was associated with the prevalence of retinopathy [odds ratio (OR) = 3.13, 95% confidence interval (CI) = 1.42-6.89, P = 0.0046, Gln/Gln vs. Gln/Arg and Arg/Arg]. This polymorphism was also associated with nephropathy (OR = 3.01, 95% CI = 1.30-6.98, P = 0.0103). There were no differences between the three PON1 genotypes (Gln/Gln, Gln/Arg, and Arg/Arg) with regard to the present disease status. Logistic regression analysis for the adjustment of other risk factors revealed that genotypes with PON1 192Arg were an independent predictor of retinopathy. No associations were found between microangiopathies and the other polymorphisms evaluated (plasminogen activator inhibitor-1, fibrinogen, and platelet glycoprotein Ibalpha). CONCLUSIONS: This study suggests that the presence of the 192Arg-allele in the PON1 gene is a genetic risk factor for microangiopathy in Type 2 diabetes mellitus.