ABCG8基因T400K多态性与胆囊结石病以及血脂水平的关系

目的:探讨人类ABCG8基因T400K多态性与胆囊结石病的关系,以及对血脂的影响。方法:对283例胆囊结石病人和212例健康人群采集静脉血,提取其基因组DNA,采用聚合酶链反应-限制性长度多态性分析ABCG8T400K多态性,并经DNA测序验证;测定血脂。结果:T400K在总体胆石组与对照组之间的分布无显著差异(21.6%比17.0%,P=0.205);但在男性胆石组中,K400频率明显高于对照组(25.9%比11.9%,P<0.01),女性中无差异(18.6%比21.6%,P=0.531)。胆石组血清低密度脂蛋白-胆固醇(2.64±0.88)mmol/L明显高于对照组(2.07±0.78)mmol/L,P<0.01。在TT纯合体胆石病人中,总胆固醇[(4.38±0.98)mmol/L比(4.02±0.83)mmol/L,P<0.05]和低密度脂蛋白-胆固醇[(2.69±0.87)mmol/L比(2.05±0.76)mmol/L,P<0.01]也较对照组显著增加;但在TK/KK中,胆石组和对照组的血脂无差异。结论:ABCG8基因T400K多态性影响胆固醇代谢,K400携带者是男性胆石病的危险因素。

胆囊黏膜ABCG5和ABCG8与胆囊胆固醇息肉关系的研究

目的:研究胆囊黏膜ABCG5和ABCG8的基因表达与胆囊胆固醇息肉发病的关系。方法:收集63例因胆囊疾患而行腹腔镜胆囊切除术患者的胆石、胆汁及部分胆囊黏膜组织,其中胆囊胆固醇息肉32例,胆囊胆固醇结石18例,对照13例(胆囊腺瘤6例,非胆固醇胆囊结石7例),分别测定胆石胆固醇含量,胆汁胆固醇、胆汁酸、磷脂的浓度,实时定量PCR检测胆囊黏膜ABCG5和ABCG8的mRNA表达。结果:胆固醇息肉组胆汁胆固醇饱和指数较对照组明显增高(P<0.01),结石组胆囊黏膜ABCG5和ABCG8的表达量较息肉组和对照组显著增高,息肉组和对照组ABCG5和ABCG8的表达量差异无统计学意义(P>0.05)。结论:胆囊黏膜ABCG5/ABCG8mRNA的相对低水平表达,可能是导致胆囊胆固醇息肉发病的重要因素之一。

ABCG5和ABCG8在胆囊胆固醇结石形成中的作用

腺苷三磷酸结合盒转运体G5和G8(ATPbindingcassettetransportG5 ,ABCG5和ATPbindingcassettetransportG8,ABCG8)位于构成管腔的细胞膜一端 ,使进入细胞内的固醇泵出到细胞外 ,参与胆固醇逆向转运 (RCT) ,在减少小肠和促进肝脏排泄固醇过程中发挥重要作用。突变后导致机体固醇蓄积 ,血浆固醇水平升高。ABCG5和ABCG8是促进胆囊胆固醇结石形成的关键因素。激动核受体LXR、RXR和FXR的途径对ABCG5和ABCG8的表达具有调控作用。

Nonsense variant of ATP8B1 gene in heterozygosis and benign recurrent intrahepatic cholestasis: A case report and review of literature

BACKGROUND Benign recurrent intrahepatic cholestasis is a genetic disorder with recurrent cholestatic jaundice due to ATP8B1 and ABCB11 gene mutations encoding for hepato-canalicular transporters.Herein,we firstly provide the evidence that a nonsense variant of ATP8B1 gene(c.1558A>T)in heterozygous form is involved in BRIC pathogenesis.CASE SUMMARY A 29-year-old male showed severe jaundice and laboratory tests consistent with intrahepatic cholestasis despite normal gamma-glutamyltranspeptidase.Acute and chronic liver diseases with viral,metabolic and autoimmune etiology were excluded.Normal intra/extra-hepatic bile ducts were demonstrated by magnetic resonance.Liver biopsy showed:Cholestasis in the centrilobular and intermediate zones with bile plugs and intra-hepatocyte pigment,Kupffer’s cell activation/hyperplasia and preserved biliary ducts.Being satisfied benign recurrent intrahepatic cholestasis diagnostic criteria,ATP8B1 and ABCB11 gene analysis was performed.Surprisingly,we found a novel nonsense variant of ATP8B1 gene(c.1558A>T)in heterozygosis.The variant was confirmed by Sanger sequencing following a standard protocol and tested for familial segregation,showing a maternal inheritance.Immunohistochemistry confirmed a significant reduction of mutated gene related protein(familial intrahepatic cholestasis 1).The patient was treated with ursodeoxycholic acid 15 mg/kg per day and colestyramine 8 g daily with total bilirubin decrease and normalization at the 6th and 12th mo.CONCLUSION A genetic abnormality,different from those already known,could be involved in familial intrahepatic cholestatic disorders and/or pro-cholestatic genetic predisposition,thus encouraging further mutation detection in this field.

ABCG5和ABCG8与胆囊结石关系的研究进展

腺苷三磷酸结合盒转运体超家族G亚家族成员ABCG5和ABCG8是腺苷三磷酸结合盒转运体家族成员,在内质网产生后定位于细胞膜上发挥作用,具有从肠内细胞分泌胆固醇到肠腔内以及从肝脏分泌胆固醇到胆汁中的功能,促成了胆汁内胆固醇的过饱和,而胆固醇过饱和是形成胆囊结石的重要病理生理改变.本文就ABCG5、ABCG8的结构、功能等与胆囊结石形成原因作一综述.

SAK-HV蛋白通过上调ABCG5/ABCG8的表达降低胆固醇的吸收

目的通过动物实验和体外细胞实验探讨SAK-HV蛋白降胆固醇的机制。方法以0.5mg/kg浓度的SAK-HV蛋白治疗高脂喂养的Apo E-/-C57小鼠,酶法检测Apo E-/-C57小鼠血脂水平,定量PCR法(real-time quantitative PCR,q PCR)和蛋白质印迹(Western blot)法检测小肠ABCG5和ABCG8 m RNA和蛋白的表达水平。100μg/ml的SAK-HV蛋白作用caco-2细胞不同时间后,NBD胆固醇作为荧光探针检测SAK-HV蛋白对caco-2细胞胆固醇吸收的影响,q-PCR和Western blot法检测SAK-HV蛋白对caco-2细胞ABCG5和ABCG8 m RNA和蛋白表达水平的影响。结果 SAK-HV蛋白可以降低高脂喂养的Apo E-/-C57小鼠的血清胆固醇水平,同时上调小肠ABCG5和ABCG8 m RNA和蛋白的表达水平。体外实验表明,SAK-HV蛋白可以抑制caco-2细胞胆固醇的吸收,同时上调ABCG5和ABCG8 m RNA和蛋白的表达水平。结论 SAK-HV蛋白通过上调ABCG5和ABCG8的表达抑制小肠胆固醇的吸收从而降低血清胆固醇水平。

中国汉族冠心病人群ABCG5/ABCG8基因rs4299376多态性及脂质水平分析

目的探究中国人群ABCG5/ABCG8基因rs4299376多态性与冠心病的相关性,并对一些相关脂质和脂蛋白水平进行研究,探究其与冠心病的关系。方法收集290例冠心病、198例非冠心病及331例健康正常人的血样,采用核酸自动提取仪提取基因组DNA,MassARRAY时间飞行质谱技术分析rs4299376基因型,并测定所有研究对象血脂水平,对比分析各组人群基因多态性及血脂水平差异。结果中国人群ABCG5/ABCG8基因rs4299376多态性在冠心病组与非冠心病组以及健康对照组之间的分布差异无统计学意义。在总体和男性患者中,脂质水平与冠心病没有相关性;但在女性患者中,冠心病患者三酰甘油(TG)及总胆固醇(TC)水平比非冠心病患者高,差异有统计学意义(TG:2.23±1.05 vs 1.84±1.03,P=0.01;TC:4.79±1.17 vs 4.36±1.03,P=0.01)。根据年龄进行分层分析,≥60岁人群中,冠心病患者高密度脂蛋白(HDL)水平比非冠心病患者低(1.09±0.23 vs 1.16±0.25,P=0.03)。结论中国人群ABCG5/ABCG8基因rs4299376多态性与冠心病可能关系不大;女性冠心病患者较非冠心病患者具有更高的TC和TG水平,60岁及以上的冠心病患者较非冠心病患者具有更低的HDL水平。

Bioinformatics Analysis of Disease Resistance Gene PR1 and Its Genetic Transformation in Soybeans and Cultivation of Multi-resistant Materials

In agricultural production,a single insect-resistant and disease-resistant variety can no longer meet the demand.In this study,the expression vector pCAMBIA-3301-PR1 containing the disease-resistant gene PR1 was constructed by means of genetic engineering,and the PR1 gene was genetically transformed to contain the PR1 gene through the pollen tube method.In CryAb-8Like transgenic high-generation T7 receptor soybean,a new material that is resistant to insects and diseases is obtained.For T2 transformed plants,routine PCR detection,Southern Blot hybridization,fluorescence quantitative PCR detection,indoor and outdoor pest resistance identification and indoor disease resistance identification were performed.The results showed that there were 9 positive plants in the routine PCR test of T2 generation.In Southern Blot hybridization,both PR1 and CryAb-8Like genes are integrated in soybeans in the form of single copies.Fluorescence quantitative PCR showed that the expression levels of PR1 and CryAb-8Like genes are different in different tissues.The average expression levels of PR1 gene in plant roots,stems,and leaves are 2.88,1.54,and 5.26,respectively.CryAb-8Like genes are found in roots,stems,and leaves.The average expression levels were 1.36,1.39,and 4.25,respectively.The insectivorous rate of the CryAb-8Like gene in outdoor plants with positive insect resistance identification was 3.78%.The disc partition method was used indoors for pest resistance identification,and the bud length of transformed plants increased significantly.The average mortality rate of untransformed plants in indoor disease resistance identification was as high as 56.66%,and the average mortality rate of plants transformed with PR1 gene was 10.00%,and disease resistance was significantly improved.Therefore,a new material with resistance to diseases and insects is obtained.

双蓣调脂汤对高胆固醇血症模型大鼠肝组织中HMGCR、ABCG5及ABCG8表达的影响

目的探讨双蓣调脂汤治疗高胆固醇血症的可能作用机制。方法32只雄性SD大鼠随机分为对照组、模型组、双蓣调脂汤组和辛伐他汀组,每组8只。除正常组给予普通饲料外,其余各组大鼠均给予高脂饲料喂养4周建立高胆固醇血症模型。双蓣调脂汤组给予双蓣调脂汤7.8 g/(kg·d)灌胃,辛伐他汀组给予辛伐他汀混悬液4 mg/(kg·d)灌胃,对照组和模型组给予等量生理盐水灌胃,每组均连续灌胃4周或8周,HE染色法观察大鼠肝组织病理变化,测定各组大鼠血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平,并采用荧光定量PCR、Western Blot、免疫组化法检测肝组织中3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)、三磷酸腺苷结合盒G5(ABCG5)和三磷酸腺苷结合盒G8(ABCG8)mRNA或蛋白表达。结果与对照组相比,模型组大鼠肝组织出现明显的脂肪变性,TC、TG及LDL-C水平均显著升高(P<0.01),肝组织中HMGCR、ABCG5和ABCG8表达升高;与模型组比较,双蓣调脂汤组肝脏脂肪变性明显减轻,TC、TG及LDL-C均明显降低(P<0.05),肝组织中HMGCR mRNA及蛋白水平显著降低(P<0.01),而ABCG5 mRNA和ABCG8 mRNA及蛋白水平显著升高(P<0.01),并且双蓣调脂汤灌胃8周比4周作用更显著(P<0.01)。结论双蓣调脂汤能减轻肝脏脂肪变性,降低高胆固醇血症大鼠血脂,其机制可能与下调HMGCR表达,同时上调ABCG5和ABCG8表达有关。

二花脸猪ABCG8基因的蛋白功能与组织表达分析

ABC转运蛋白8(ABCG8)基因与家畜抗逆性相关,为探究猪ABCG8编码的蛋白功能及其在各组织中的表达,通过PCR技术克隆二花脸猪ABCG8基因,使用在线生物信息学方法分析ABCG8质结构与功能,利用qRT-PCR检测其组织差异性表达分析。结果表明:该蛋白子式为C3638H5712N982O1027S35,编码730个氨基酸,分子量为80761.43 kD,pI值为8.73,GRAVY值为0.071,属于疏水蛋白。该蛋白存在109个潜在的N-磷酸化位点和6个O-糖基化位点,不存在信号肽序列,二级结构主要由α螺旋(43.01%)、β-转角(6.16%)、延伸链(14.52%)和无规则卷曲为(36.30%)组成,主要定位在细胞膜和内质网,是定位于细胞膜上的多次跨膜蛋白,可能与ABCG5、NPC1L1、CYP7A1、NR1H3、SCARB1、SREBF2、APOA1、NR1H2、SQLE、NR1H4等蛋白存在相互作用关系。此外,ABCG8基因在二花脸猪各组织中的表达谱分析表明,ABCG8基因在肝脏组织中的表达量最高,小肠次之,在其他组织中几乎不表达。研究结果为进一步研究ABCG8在猪生长性能和肉质性能调控中的机理研究奠定了基础。

Cloning of TaCYP707A1 Gene that Encodes ABA 8′-Hydroxylase in Common Wheat (Triticum aestivum L.)

The plant hormone abscisic acid （ABA） regulates many important physiological and developmental processes in plants. The objective of this study was to clone the ABA 8′-hydroxylase gene in common wheat. In the present study, we used the eDNA sequence of barley HvCYP707A1 gene （GenBank accession no. AB239299） as a probe for BLAST search against the common wheat （Triticum aestivum L.） EST database in GenBank. All wheat ESTs sharing high similarity with the reference gene were subjected to contig assembly. Primers were designed based on the constructed contigs to clone the wheat CYP707A1 gene, designated as TaCYP707A1. The genomic DNA sequence of TaCYPTO7A1 gene comprised five exons and four introns, with a size of 2225 bp. The corresponding cDNA sequence of TaCYP707A1 was 1737 bp, containing an open reading frame （ORF） of 1431 bp, a 42-bp 5′-untranslated region （UTR） and a 264-bp 3′UTR, with 94.9% of identical sequences to HvCYP707A1 gene （AB239299）. The neighbor joining tree indicated that the deduced amino acid sequences of TaCYP707A1 gene was highly similar to those of barley and rice. The TaCYP707A1 gene was located on chromosome 6BL using a set of Chinese Spring nullisomic-tetrasomic lines and ditelosomic line 6BS. These results will be of high importance in understanding of molecular mechanism of ABA catabolism.

The Effects of Dwarfing Genes (Rht-B1b, Rht-D1b, and Rht8) with Different Sensitivity to GA_3 on the Coleoptile Length and Plant Height of Wheat

Understanding the effects of wheat dwarfing genes on the coleoptile length and plant height is crucial for the proper utilization of dwarfing genes in the improvement of wheat yield. Molecular marker analysis combined with pedigree information were used to classify wheat cultivars widely planted in major wheat growing regions in China into different categories based on the dwarfing genes they carried. The effects of the dwarfing genes with different sensitivity to gibberellins （GA3） on the coleoptile length and plant height were analyzed. Screening of 129 cultivars by molecular marker analysis revealed that 58 genotypes of wheat contained the dwarfing gene Rht-B1b, 24 genotypes of wheat contained Rht-D1b gene and 73 genotypes of wheat possessed Rht8 gene. In addition, among these 129 cultivars, 35 genotypes of wheat cultivars contained both Rht-B1b and Rht8 genes and 16 genotypes of wheat cultivars contained both Rht-D1b and Rht8 genes. Wheat cultivars with the dwarfing genes Rht-B1b or Rht-D1b were insensitive to GA3, while the cultivars with the dwarfing gene Rht8 were sensitive to GA3. Most of the wheat genotypes containing combination of Rht8 gene with either Rht-B1b or Rht-D1b gene were insensitive to GA3. The plant height was reduced by 24.6, 30.4, 28.2, and 32.2%, respectively, for the wheat cultivars containing Rht-B1b, Rht-D1b, Rht-B1b ＋ Rht8, and Rht-D1b ＋ Rht8 genes. The plant height was reduced by 14.3% for the wheat cultivar containing GA3-sensitive gene Rht8. The coleoptile length was shortened by 25.4, 31.3, 28.4 and 31.3%, respectively, in the wheat cultivars containing Rht-B1b, Rht-D1b, Rht-B1b ＋Rht8 and Rht-D1b ＋ Rht8 genes, while the coleoptile length was shortened only by 6.2% for the wheat cultivar containing Rht8 gene. We conclude that GA3-insensitive dwarfing genes （Rht-B1b and Rht-D1b） are not suitable for the wheat improvement in dryland because these two genes have effect on reducing both plant height and coleoptile length. In contrast, GA3- sensitive dwarfing gene （Rht8） is a relatively ideal candidate for the wheat improvement since it significantly reduces the plant height of wheat, but has less effect on the coleoptile length.

Cloning and Expression of a Chitinase Gene from Serratia marcescens Strain C8-8

A 1 692 bp long chitinase-encoding ch/A gene was cloned from the genomic DNA of Serrat/a marcescens strain C8-8 by PCR, which was speculated to en- code a 563 aa long polypeptide chain with molecular weight of about 60.9 kD. Homolog analysis showed that the chiA gene sequence cloned from C8-8 shared the highest similarity with cMA sequences from Serrat/a maresscens strains 141 （ DQ 990373.1 ） and 14041 （ DQ 493896. 1 ）, which reached 99%. Domain analysis showed that N-termlnal （23 aa） of the chiA gene cloned from C8-8 harbored typical signal peptide sequence, while C-telminal harbored the other two domains, in- eluding the PKD region （73 aa） and chitinase catalytic region （387 aa）. The PCR fragment was digested with restriction endonucleases and cloned into plasmid pET28a. The recombinant plasmid pET＇28a-ch/A was firstly transformed into Escherichia coli DI-I5 , and then transformed into expression host E. coli DH3 to express ch/A gene. The recombinant strain DH3 chiA could produce transparent hydrolysis circles on the colloidal chitin plate induced by isopropyl-l-thiogalactopyranoside （IFrG）. SDS-PAGE electrophoresis analysis showed that, a protein with relative molecular weight of about 60 kD was expressed by the recombinant strain DH3 chiA, which was consistent with the except molecular weight. After initial purification, biological activity test showed that the recombinant expression product could hydrolyze chitin, which produced transparent hydrolysis circles on the colloidal chitin plates. Results indicated that chiA gene from Serrat/a marcescens strain C8-8 had biological functions and could be utilized as a potential biological control factor.

Interleukin-8 gene polymorphism is associated with acute coronary syndrome in a Han Chinese population

Background Acute coronary syndrome(ACS) is one of the most common forms of heart diseases.Recent studies have revealed that interleukin(IL)-8 plays a kev role in the development of atherosclerosis plaque and its complications, but the relationship of its common variants with ACS has not been extensively studied.Methods We tested the hypothesis that variants in IL-8-251 A/T was associated with susceptibility to ACS and its recurrence in a Chinese case-control study comprising 675 patients with ACS and 636 control subjects and replicated the investigation in an independent study comprising 360 cases and 360 control subjects. The plasma concentration of IL-8 was measured by enzyme-linked immunosorbent assay.Results IL-8 -251A】T poly-morphism was associated with increased susceptibility to ACS (P=0.004;OR=1.30 CI:1.12-1.53).Replication in the second study yielded similar results.IL-8 -251 A/T may affect the expression of IL-8 by the evidence that augmented IL-8 production revealed in serum of the AMI patients by ELISA. Conclusions IL-8 -251 A/T polymorphism is associated with ACS risk in Chinese Han population and An allele of IL-8- 251A/T may be an independent predictive factor.

OsABA8ox2, an ABA catabolic gene, suppresses root elongation of rice seedlings and contributes to drought response

In rice, OsABA8ox encodes abscisic acid(ABA) 8′-hydroxylase, which catalyzes the committed step of ABA catabolism. The contribution of ABA catabolism in root development remains unclear. We investigated the role of OsABA8ox2 in root growth and development and drought response. GUS staining results showed that OsABA8ox2 was expressed mainly in roots at seedling stage and was strongly expressed in the meristematic zone of the radicle. OsABA8ox2 expression in roots was markedly decreased after 0.5 h polyethylene glycol(PEG) treatment and increased after 0.5 h rehydration, implying that OsABA8ox2 is a drought-responsive gene.OsABA8ox2 knockout mediated by the CRISPR-Cas9 system increased drought-induced ABA and indole-3-acetic acid accumulation in roots, conferred increased ABA sensitivity, and promoted a more vertically oriented root system architecture(RSA) beneficial to drought tolerance.OsABA8ox2 overexpression suppressed root elongation and increased stomatal conductance and transpiration rate. Consequently, OsABA8ox2 knockout dramatically improved rice drought tolerance, whereas OsABA8ox2 overexpression seedlings were hypersensitive to drought stress,suggesting that OsABA8ox2 contributes to drought response in rice. Compared with wild type,functional leaves of OsABA8ox2 knockout seedlings showed higher ABA levels, whereas overexpression lines showed lower ABA levels, suggesting that OsABA8ox2, as an ABA catabolic gene, modulates ABA concentration through ABA catabolism. OsABA8ox2 and OsABA8ox3 were both localized in the endoplasmic reticulum. Together, these results indicate that OsABA8ox2 suppresses root elongation of rice seedlings, increases water transpiration, and contributes to drought response through ABA catabolism, and that OsABA8ox2 knockout dramatically improves rice drought tolerance. They highlight the key role of ABA catabolism mediated by OsABA8ox2 on root growth and development. OsABA8ox2, as a novel RSA gene, would be a potential genetic target for the improvement of rice drought tolerance.

Cloning of Promoter of Chinese Bean GRP 1.8 Gene and Characterization of Its Function in Transgenic Tobacco Plants

In order to learn the expression pattern of GRP1 8(glycine rich protein) gene promoter in transgenic plants and to explore its potential application in plant genetic engineering for vascular specific expression of interested genes, GRP 1 8 promoter was amplified by PCR from Chinese bean genomic DNA. The intermediate vector was constructed by inserting vascular specific expression promoter of GRP 1 8 gene in vector pBI 101. The regenerated tobacco plants obtained were analyzed by PCR to select the putative transgenic plants. The histochemical localization of GUS( β D glucosidase) activity indicates that as for that of GRP 1 8 promoter we can confer the vascular specific expression of GUS gene.

Mycobacterium bovis BCG as a Delivery System for the dtb Gene Antigen from Diphtheria Toxin

Diphtheria is a fulminant bacterial disease caused by toxigenic strains of Corynebacterium diphtheriae whose local and systemic manifestations are due to the action of the diphtheria toxin (DT). The vaccine which is used to prevent diphtheria worldwide is a toxoid obtained by detoxifying DT. Although associated with high efficacy in the prevention of disease, the current anti-diphtheria vaccine, one of the components of DTP (diphtheria, tetanus and pertussis triple vaccine), may present post vaccination effects such as toxicity and reactogenicity resulting from the presence of contaminants in the vaccine that originated during the process of production and/or detoxification. Therefore, strategies to develop a less toxic and at the same time economically viable vaccine alternatives are needed to improve existing vaccines in use worldwide. In this study, the Moreau substrain of BCG which is used in Brazil as a live vaccine against human tuberculosis was genetically modified to carry and express the gene encoding for the diphtheria toxin fragment B (DTB). As such, the DNA sequence encoding the dtb gene was cloned into the pUS977 shuttle vector for cytoplasmic expression and successfully introduced into BCG cells by electroporation. Mice immunized with recombinant BCG expressing DTB showed seroconversion with the detection of specific antibodies against DTB. Also, rBCGs stably expressing DTB persisted up to 60 days in the absence of selective pressure in mice and cell viability did not change significantly during the period tested. Finally, immune sera from BALB/c mice vaccinated with rBCGpUS977dtbPW8 were preliminarily tested for their capacity of neutralizing the diphtheria toxin in the Vero Cells assay.

A correlation study between ITGA6 gene,chromosome 8q24,MSMB genes and prostate cancer

Objective To explore the correlation between IT-GA6 gene ( rs12621278, G ) , MSMB gene ( rs10993994,T) ,chromosome 8q24 9 ( rs10086908, T) and prostate cancer ( PCa) in Beijing residents,and to explore the correlation between genotype and pheno-

Inflammatory cytokine gene polymorphisms increase the risk of atrophic gastritis and intestinal metaplasia

AIM: To investigate the effects of interleukin-8 (IL-8 ), macrophage migration inhibitory factor (MIF ) gene polymorphisms, Helicobacter pylori (H. pylori ) infection, on the risk of developing severe chronic atrophic gastritis (SCAG) and intestinal metaplasia (IM). METHODS: A total of 372 cases were selected from a cohort study in Linqu County, a high risk area for gastric cancer (GC) in northern China. To obtain a sufficient group size, patients with normal or superficial gastritis were included. Based on an average follow-up period of 56 mo, the 372 cases were divided into no progres-sion group (no histological progression from normal or superficial gastritis, n = 137), group Ⅰ (progressed from normal or superficial gastritis to SCAG, n = 134) and group Ⅱ (progressed from normal or superficial gastritis to IM, n = 101). IL-8 , MIF gene polymorphisms were detected by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis and DNA sequencing. RESULTS: An increased risk of SCAG was found in subjects with IL-8-251 AA genotype [odds ratio (OR) = 2.62, 95% CI: 1.23-5.72] or IL-8-251 A allele carriers (AA + AT) (OR = 1.81, 95% CI: 1.06-3.09). An elevated risk of IM was found in subjects with IL-8-251 AT genotype (OR = 2.27, 95% CI: 1.25-4.14) or IL-8-251 A allele carriers (OR = 2.07, 95% CI: 1.16-3.69). An increased risk of SCAG was found in subjects with MIF-173 GC genotype (OR = 2.36, 95% CI: 1.38-4.02) or MIF-173 C allele carriers (GC + CC) (OR = 2.07, 95% CI: 1.21-3.55). An elevated risk of IM was found in subjects with MIF-173 CC genotype (OR = 2.27, 95% CI: 1.16-4.46) or MIF-173 C allele carriers (OR = 3.84, 95% CI: 1.58-9.34). The risk of SCAG and IM was more evident in subjects carrying IL-8-251 A allele (OR = 6.70, 95% CI: 1.29-9.78) or MIF-173 C allele (OR = 6.54, 95% CI: 2.97-14.20) and positive for H. pylori infection. CONCLUSION: IL-8-251 and MIF-173 gene polymorphisms are significantly associated with the risk of SCAG and IM in a population with a high risk of GC in Linqu County, Shandong Province, China.