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gene polymorphisms of interleukin-28, p21-activated protein kinases 4, and response to interferon-α based therapy in Chinese patients with chronic hepatitis B

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Chinese Medical Journal 2013年第9期126卷 1726-1731页

作者： YU Feng-xue ZHANG Xiao-lin WANG Yan-ping MA Ning DU Hong MA Jian-min LIU Dian-wu Department of Science and Technology The Second Hospital of Hebei Medical University Shijiazhuang Hebei 050000 China Department of Epidemiology Hebei Medical University Shijiazhuang Hebei 050071 China Department of Operating Room Bethune International Peace Hospital of People's Liberaton Army Shijiazhuang Hebei 070010 China Medical Department Shunping County Hospital Shijiazhuang Hebei 070010 China

Background Peg-lnterferon-a treatment is expensive and associated with considerable adverse effects, selection of patients with the highest probability of response is essential for clinical practice. The objective of this study was to assess the relationship between the gene polymorphisms of interleukin-28 （IL-28）, p21-activated protein kinase 4 （PAK4） and the response to interferon treatment in chronic hepatitis B patients. Methods Two hundred and forty interferon-naive treatment HBeAg seropositive chronic hepatitis B patients were enrolled in the present prospective nested case-control study. Peripheral blood samples were collected, including 92 with favorable response and 148 without response to the interferon treatment. Rs8099917, rs12980602, and rs9676717 SNP was genotyped using matrix assisted laser desorption/ionization time of flight mass spectrometry （MALDI-TOF MS）. Results IL-28 genotype was not associated with response to interferon treatment （OR for GT/GG vs. TT, 0.881 （95% CI 0.388-2.002）; P=0.762; OR for CT/CC vs. TT, 0.902 （95% CI 0.458-1.778）; P=-0.766）. Rs9676717 in PAK4 genotype was independently associated with the response （OR for CT/CC vs. TT, 0.524 （95% CI 0.310-0.888）; P=0.016）. When adjusting for age, gender, smoking, drinking, levels of hepatitis B virus DNA, and alanine aminotransferase （ALT）, rs9676717 genotype TT appeared to be associated with a higher probability of response for interferon treatment （OR, 0.155 （95% CI 0.034-0.700）; P=0.015）. Conclusion Genotype TTfor rs9676717 in PAK4 gene and no drinking may be predictive of the interferon-a treatment success.

关键词： chronic hepatitis B gene polymorphisms interleukin-28 interferon-a p21-activated protein kinase 4

Association between ADIPOQ gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2017年第6期16卷 602-609页

作者： Chao Cen Hai-Xing Fang Song-Feng Yu Ji-Min Liu Yuan-Xing Liu Lin Zhou Jun Yu Shu-Sen Zheng Department of Hepatobiliary and Pancreatic Surgery Key Laboratory of Combined Multi-organ TransplantationMinistry of Public HealthCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of Medicine Department of Hepatobiliary Surgery the First People's Hospital of Fuyang Department of Pathology and Molecular Medicine Faculty of Health SciencesMcMaster University

BACKGROUND:New-onset diabetes after transplantation(NODAT) has become one of the major factors that affect the overall survival and long-term life quality in liver transplantation(LT) recipients. Previous studies found that the serum adiponectin concentration of diabetic patients is significantly lower than that of healthy subjects. Adiponectin regulates the blood glucose level by increasing body sensitivity to insulin through various mechanisms. In this study, we aimed to investigate the impact of diabetes related gene polymorphisms on the development of NODAT in liver ***:A total of 256 LT patients in a single-center were selected retrospectively for the study. Genomic DNA was extracted from explanted liver tissues, and tested for twelve diabetes mellitus associated single nucleotide polymorphisms by Sequenom Mass ARRAY. Modified clinical models in predicting NODAT were established and ***:The GG genotype of ADIPOQ rs1501299 gene polymorphism was significantly more frequent in NODAT than non-NODAT LT patients(56% vs 39%, P=0.014). Dominant model(GG vs GT+TT, P=0.030) and recessive model(GT+GG vs TT, P=0.005) also confirmed the genotype distribution difference between NODAT and non-NODAT groups. Age(OR=1.048, P=0.004), BMI(OR=1.107, P=0.041), and blood tacrolimus level at 1-month LT(OR=1.170, P=0.003) were clinical independent risk factors of NODAT. Furthermore, rs1501299 could improve the ability of clinical model in predicting NODAT(AUROC=0.743, Pgene polymorphism is associated with an increased risk of NODAT, which should be added to the clinical models in predicting the occurrence of NODAT in LT recipients.

关键词： ADIPOQ gene polymorphisms diabetes mellitus liver transplantation

Associations between gene polymorphisms of thymidylate synthase with its protein expression and chemosensitivity to 5-fluorouracil in pancreatic carcinoma cells

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Chinese Medical Journal 2011年第2期124卷 262-267页

作者： ZHANG Qiang ZHAO Yu-pei LIAO Quan HU Ya XU Qiang ZHOU Li SHU Hong Department of general Surgery Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730 China

Background Thymidylate synthase （TS） is a key regulatory enzyme for de novo DNA *** activity is also an important determinant of the response to chemotherapy with fluoropyrimidine prodrugs,and its expression may be affected by gene *** this study,we investigated the associations between polymorphisms of the TS gene and its protein expression,and the implications on the efficacy of 5-fluorouracil （5-FU） in pancreatic cancer *** Genotypes based on the 28-bp TS tandem repeat for pancreatic cell lines were determined by electrophoretic analysis of PCR products.A single nucleotide polymorphism （SNP） at nucleotide 12 of the second 28-bp repeat of the 3R allele was determined by nucleotide *** chemosensitivity of pancreatic carcinoma cells to 5-FU in vitro was evaluated using Cell Counting Kit-8 （CCK-8）.TS protein expression was analyzed by Western *** Seven pancreatic carcinoma cell lines had different genotypes in terms of the 28-bp TS tandem repeat,as follows：homozygous 2R/2R （T3M4 and BxPC-3 cells）,heterozygous 2R/3R （AsPC-1,Capan-1,and SU86.86）,and homozygous 3R/3R （PANC-1 and COLO357）.The optical density ratio of genotypes 3R/3R,2R/2R and 2R/3R was 1.393±0.374,0.568±0.032 and 0.561±0.056,*** with the 2R/3R or 3R/3R genotypes were further analyzed for the G to C SNP at nucleotide 12 of the second 28-bp repeat of the 3R allele,yielding heterozygous 2R/3Rc （AsPC-1,Capan-1,and SU86.86）,homozygous 3Rg/3Rg （COLO357） and homozygous 3Rc/3Rc （PANC-1）.The optical density ratio of homozygous 3Rg/3Rg cells and homozygous 3Rc/3Rc cells was 1.723±0.062 and 1.063±0.134,respectively,and this difference was statistically significant （P 〈0.05）.Cells with the 2R/2R and 2R/3R genotypes of TS were hypersensitive to 5-FU in vitro as compared with those with the 3R/3R *** polymorphisms in the TS gene influenced its protein expression and affected sensitivity of 5-FU in seven pancreatic cancer cell ***

关键词： thymidylate synthase gene polymorphisms pancreatic carcinoma

Correlation of estrogen receptor alpha gene polymorphisms and bone mineral density in Chinese women with chronic periodontitis

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Chinese Medical Journal 2010年第22期123卷 3262-3267页

作者： ZHANG Xuan DAI Juan LONG Yin WU Hao LI Xiao-juan DING Yin Department of Orthodontics School of Stomatology Fourth Military Medical University Xi'an Shaanxi 710032 China Department of Traditional Chinese Medicine Fourth Military Medical University Xi'an Shaanxi 710032 China Laboratory of Bone Density Fourth Military Medical University Xi'an Shaanxi 710032 China Xijing Hospital Statistical Analysis Laboratory Fourth Military Medical University Xi'an Shaanxi 710032 China Department of Stomatology Chinese People's Liberation Army General Hospital Beijing 100853 China

Background Periodontitis and osteoporosis are one of the frequently encountered diseases in post-menopausal women. Estrogen receptors （ERs） regulated bone metabolism. To investigate the possible effect of ER-elpha （a） gene polymorphisms on bone mineral density （BMD） in pre- and post-menopausal Chinese women with chronic periodontitis （CP）, we provided sufficient quantitative information concerning the correlation between ER gene polymorphisms and BMD in periodontitis. Methods Sixty-five post-menopausal and eighty pre-menopausal CP women, and sixty post-menopausal healthy individuals were recruited in this study. Genomic DNA was extracted from oral mucosa swab sample of each subject by the Chelex-100 method. Determination of the ER-a polymorphisms was performed by polymerese chain reaction-restriction fragment length polymorphism （PCR-RFLP） technique with Xbal and Pvull enzyme. The index for periodontal examination includes clinical attachment loss （CAL） and probing pocket depth （PPD）. BMD was measured by dual-energy X-ray absorptiometry （DEXA）. Results There were no significant differences between the ER-α genotypes of Pvull and Xbal and BMD in post-menopausal and pre-menopausal CP patients, respectively （P 〉0.05）. However, there was association between pre- and post-menopausal CP patients at BMD of lumbar spine L2-L4 （P=0.027） and Ward＇s BMD （P=0.004）. Furthermore, the post-menopausal CP women who carried Pvull TT genotype presented significantly lower Ward＇s BMD than the pre-menopausal CP women （P=-0.007）, meanwhile, the post-menopausal CP women who carried Xbal AA genotype presented significantly lower spine L2-L4 BMD than the pre-menopausal CP women （P=0.003）. Conclusions ER-α gene polymorphisms may be a susceptible indicator for BMD variation of lumbar spine L2-L4 and Ward in Chinese pre- and post-menopausal women patients with CP.

关键词： estrogen receptor-a gene polymorphisms chronic periodontitis bone mineral density pre-menopausal post-menopausal osteoporosis

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

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World Journal of Gastroenterology 2010年第14期16卷 1788-1794页

作者： Li, Zhong-Wu Wu, Ying Sun, Yu Liu, Lu-Ying Tian, Meng-Meng Feng, Guo-Shuang You, Wei-Cheng Li, Ji-You Peking Univ Key Lab Carcinogenesis & Translat Res Minist Educ Dept PatholSch OncolBeijing Canc Hosp & Inst Beijing 100142 Peoples R China Peking Univ Key Lab Carcinogenesis & Translat Res Minist Educ Dept EpidemiolSch OncolBeijing Canc Hosp & Inst Beijing 100142 Peoples R China

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

关键词： Chronic atrophic gastritis gene polymorphisms Helicobacter pylori Interleukin-8 Intestinal metaplasia Macrophage migration inhibitory factor

Correlating interleukin-10 promoter gene polymorphisms with human cerebral infarction onset

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Neural Regeneration Research 2015年第11期10卷 1809-1813页

作者： Xin-hong Jiang Ke-xu Lin Yi-xian Zhang Rong-hua Chen Nan Liu Department of Rehabilitation Union Hospital Fujian Medical University Department of Emergency Union Hospital Fujian Medical University Department of Neurology Union Hospital Fujian Medical University

Evidence suggests that interleukin-10（IL-10） deficiency exacerbates inflammation and worsens the outcome of brain ischemia. In view of the critical role of the single nucleotide polymorphic sites-1082（A/G） and-819（C/T） in the promoter region of the IL-10 gene, we hypothesized that they are associated with cerebral infarction morbidity in the Chinese Han population. We genotyped these allelic gene polymorphisms by amplification refractory mutation system-polymerase chain reaction methods in 181 patients with cerebral infarction（cerebral infarction group） and 115 healthy subjects（control group）. We identified significant differences in genotype distribution and allele frequency of the IL-10-1082 A/G allele between cerebral infarction and control groups（χ2 = 6.643, P = 0.010）. The IL-10-1082 A allele frequency was significantly higher in the cerebral infarction group（92.3%） than in the control group（86.1%）（P = 0.015）. Moreover, cerebral infarction risk of the AA genotype was 2-fold higher than with the AG genotype（OR = 2.031, 95%CI： 1.134-3.637）. In addition, AA genotype together with hypertension was the independent risk factor of cerebral infarction（OR = 2.073, 95%CI： 1.278-3.364）. No statistical difference in genotype distribution or allele frequency of IL-10-819 C/T was found between cerebral infarction and control groups（P 〉 0.05）. These findings suggest that the IL-10-1082 A/G gene polymorphism is involved in cerebral infarction, and increased A allele frequency is closely associated with occurrence of cerebral infarction.

关键词： neural regeneration IL-IO promoter gene polymorphisms ischemic stroke geneticsusceptibility inflammation immune response ischemia/ reperfusion injury neural regeneration

Inhibition of TNF-alpha secretion from peripheral bloodmonocular cells by triptolid is associated with TNF-alpha-308gene polymorphisms in rheumatoid arthritis patients

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Frontiers of Medicine 2010年第2期4卷 220-224页

作者： Xiu-Liang TAO Sheng-Hao TU Ri-Bo XIONG Yong-Hong HU Department of Integrated Traditional Chinese and Western Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

This study examined the inhibitory effect of triptolid(TP)on tumor necrosis factor-α(TNF-α)secreted from peripheral blood monocular cells(PBMCs)and the association of the inhibitory effect with TNF-α-308 gene polymorphisms in rheumatoid arthritis(RA)*** polymorphism at A-G site 308 in the promoter region of TNF-αgene was detected in 42 RA patients by using allele speciﬁc polymerase chain reaction(AS-PCR)*** were harvested from these patients and treatedﬁrst with lipopolysaccharides(LPS)and then with different doses of TP(1,5.4 and 15 ng/mL).The TNF-αlevel in the supernatants was measured by enzyme-linked immuno-sorbent assay(ELISA).The results showed that TNF-αlevel in the supernatants of TP(1 ng/mL)-treated PBMCs was decreased by 3.80%and 4.91%,respectively,in the patients with AA and AG genotypes,when compared with those treated with LPS alone(P>0.05).Moreover,the TNF-αlevel in the patients with GG genotype was reduced by 20.74%(P0.05).It was concluded that gene polymorphism at TNF-α-308 sites may relate to the secretion of TNF-αin RA *** has different inhibitory effects on the secretion of TNF-αin the patients harboring different genotypes,which may be one of the reasons for individual variation in response to TP.

关键词： arthritis,rheumatoid molonuclear cells tumor necrosis factor gene polymorphisms triptolid

Research progress of the relationship between angiotensinogen gene polymorphisms and coronary heart disease

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South China Journal of Cardiology 2011年第1期12卷 71-76页

作者： WANG Yu-Jing PAN Yan Cardiovascular Department The First Affiliated Hospital ofYangtze University Jingzhou Hubei 434000 China Medical College of Yangtze University Jingzhou Hubei 434000China

Coronary heart disease （CHD） is a major health problem in many countries and its pathogenesis is not yet fully understood, contributing to significant morbidity and mortality. Accumulated evidence manifest clearly that CHD is determined by a complex interplay of genetic and environmental factors. Many clinical data have showed that the renin-angiotensin system （RAS） hypertension and CHD involved in many cardiovascular diseases, such as Angiotensinogen （AGT） is the key components of the RAS system, and two gene polymorphisms of AGT had been detected of the CHD risk： M235T and T174M. This article reviews the effects of AGT gene polymorphisms on the CHD.

关键词： angiotensinogen coronary heart disease gene polymorphisms

Association ofALOX5,LTA4H and LTC4S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China

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World Journal of Emergency Medicine 2013年第1期4卷 32-37页

作者： Gan-nan Wang Jin-song Zhang Wei-juan Cao Hao Sun Jing Zhang Yao Wang Hang Xiao Emergency Department First Affiliated Hospital of Nanjing Medical University Laboratory of Neurotoxicology School of Public HealthNanjing Medical University

BACKGROUND:genetic variations of the 5-lipoxygenase activating protein and leukotriene A4 hydrolase genes that confer an increased risk of ischemic stroke have implicated the family of leukotrienes as potential mediators of ischemic *** study aimed to explore the association of ALOX5,LTA4 H and LTC4 S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east ***:This case-control study consisted of 690 patients with ischemic stroke and 690 *** of ALOX5 rs2029253 A/G,LTA4 H rs6538697 T/C,and LTC4 S rs730012 A/C were genotyped by the polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP) *** multivariate logistic regression model was used to exclude the effects of conventional risk factors on ischemic ***:Carriers of C allele in rs730012 were more susceptible to ischemic stroke(OR:1.37;95%CI:1.08-1.73;P=0.009).The rs2029253 GG genotype showed a risk-reducing effect on ischemic stroke(OR:0.72;95%CI:0.55-0.93;P=0.013) while the rs6538697 CC genotype had an increased risk of ischemic stroke(OR:1.77;95%CI:1.09-2.89;P=0.022).The rs730012 variant was not associated with ischemic stroke risk after adjusting confounding factors(P>0.05).CONCLUSION:The present study suggested that gene polymorphisms in the leukotrienes pathway may exert influences,with independent genetic effects,on ischemic stroke susceptibility in a cohort of Chinese in east China.

关键词： Leukotrienes gene polymorphisms Risk factors Ischemic stroke