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LOD score exclusion analyses for candidate disease susceptibility genes using case-parents design

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Progress in natural Science:Materials International 2006年第1期16卷 30-38页

作者： DEnG Hongwen1,2,3 and GAO Guimin2,4 (1.Laboratory of Molecular and statistical Genetics, College of Life sciences, Hunan normal university, Changsha 410081, China 2.osteoporosis research center, creighton university medical center, omaha ne 68131, usa 3. department of biomedical sciences, creighton university, omaha ne 68131, usa 4. Virginia Bioin format ics Institute and department of statistics, Virginia Polytechnic Institute and state university, Blacksburg VA 24061-0315, usa) [a]Laboratory of Molecular and statistical Genetics College of Life Sciences Human National University Changsha China [b]osteoporosis research center Creighton University Medical Center Omaha NE USA [c]department of biomedical sciences Creighton University Omaha NE USA [d]Virginia Bioinformatics Institute and department of statistics Virginia Polytechnic Institute and State University Blacksburg VA USA

the focus of almost all the association studies of candidate genes is to test for their importance. We recently developed a LOD score approach that can be used to test against the importance of candidate genes for complex diseases and quantitative traits in random samples. As a complementary method to regular association analyses, our LOD score approach is powerful but still affected by the population admixture, though it is more conservative. To control the confounding effect of population heterogeneity, we develop here a LOD score exclusion analysis using case-parents design, the basic design of the transmission disequilibrium test (TDT) approach that is immune to population admixture. In the analysis, specific genetic effects and inheritance models at candidate genes can be analyzed and if a LOD score is ≤ - 2. 0, the locus can be excluded from having an effect larger than that specified. Simulations show that this approach has reasonable power to exclude a candidate gene having small genetic effects if it is not a disease susceptibility locus (DSL) with sample size often employed in TDT studies. Similar to association analyses with the TDT in nuclear families, our exclusion analyses are generally not affected by population admixture. the exclusion analyses may be implemented to rule out candidate genes with no or minor genetic effects as supplemental analyses for the TDT. the utility of the approach is illustrated with an application to test the importance of vitamin D receptor (VDR) gene underlying the differential risk to osteoporosis.

关键词： association studies candidate genes case-parents design disease susceptibility locus exclusion mapping LOD score.

Association between VDR Apal Polymorphism and Hip Bone Mineral Density Can Be Modified by Body Mass Index:A study on Postmenopausal Chinese Women

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Acta Biochimica et Biophysica Sinica 2005年第1期 61-67页

作者： Hong XUI~(1,2) Dong-Hai XIOnG~3 Fu-Hua XU~3 Yuan-Yuan ZHAnG~3 Shu-Feng LEI~1 Hong-Wen DEnG~(1,3*) ~1Laboratory of Molecular and statistical Genetics,College of Life sciences,Hunan normal university.Changsha 410081,China ~2 department of Physiology,Jiangxi medical College,nanchang 330006,China ~3 osteoporosis research center and department of biomedical sciences,creighton university medical center,omaha,ne 68131,usa

osteoporosis is a major public health problem for old *** factors are considered tobe major contributors to the pathogenesis of postmenopausal *** vitamin D receptor(VDR)gene is a prominent candidate gene for the regulation of postmenopausal bone mass;however,despite exten-sive studies,controversy remains regarding its association with postmenopausal body mineral density(BMD)*** this study,a total of 260 healthy postmenopausal Chinese women were genotyped at the VDRApaI locus using polymerase chain reaction(PCR)-restriction fragment length polymorphism (RFLP).Rawhip BMD was significantly associated with VDR ApaI polymorphism with and without adjusting for age(P=0.015 and 0.040,respectively).this genetic effect can explain 3.32% of hip BMD ***,the significant association vanished after correcting for both age and body mass index(BMI)(P=0.169).Inaddition,we observed a significant association between VDR ApaI polymorphism with unadjusted BMI(P=0.042)or BMI adjusted for age(P=0.049).the raw hip BMD was also found to be significantly corre-lated with BMI(r=0.517,P=0.0001),with BMI explaining 26.35% of the variation of hip *** of thesefacts prompt us to conclude that the significant association between the VDR ApaI genotype and hip BMDmay be modified by BMI in postmenopausal Chinese *** findings may partially explain the earlierinconsistent association results concerning the VDR gene and BMD,and highlight the importance of incorpo-rating covariates such as BMI into osteoporosis association studies.

关键词： body mass index(BMI) bone mineral density(BMD) genetic association osteoporosis vitamin D receptor(VDR)gene

Tanshinone prevents cancellous bone loss induced by ovariectomy in rats

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Acta Pharmacologica Sinica 2004年第05期25卷 136-142页

作者： Liao CUI2,3, Tie WU3, Yu-yu LIU3, Yi-feng DEnG4, Chun-mei AI4, Huai-qing CHEn22Institue of biomedical Engineering, West China medical center, Sichuan university, Chengdu 610041, China 3department of Pharmacology, 4Guangdong Key Laboratory for research and Development of natural Drugs,Guangdong medical College, Zhanjiang 524023 China Institue of biomedical Engineering West China Medical Center Sichuan University department of Pharmacology Guangdong Key Laboratory for Research and Development of Natural Drugs Guangdong Medical College

AIM: To investigate the skeletal effects of total tanshinone in ovariectomized rats by analyzing cancellous bonehistomorphometry of fourth lumbar vertebrae (LV4) and proximal tibial metaphyses (PTM). MEthODS: Four-month-old Sprague-Dawley female rats were sham-operated and treated with vehicle or ovariectomized and treatedwith either vehicle, total tanshinone (200 mgkg-1d-1, equivalent to 35 gkg-1d-1 of tanshinone II A and 16 mgkg -1d-1 ofcryptotanshinone), or 17a-ethynylestradiol (30 gkg-1d-1 as positive treatment group) starting one day post-sur-gery for 10 weeks. Double in vivo fluorochrome labeling was administered to all rats. the undecalcified longitu-dinal LV4 and PTM sections were cut and stained with Goldners Trichrome (4-m thickness) or unstained (8-mthickness) for the bone histomorphometric analysis. RESULTS: A significant decrease in trabecular bone volume(BV/TV) and trabecular number (Tb.n) and a significant increase in osteoclast surface (OCS/BS) and mineralizingsurface (MS/BS) were found in both LV and PTM of vehicle-treated OVX rats compared with sham *** completely prevented the decreases in BV/TV and Tb.n and the increase in OCS/BS in the LV4, andpartially prevented the decreases in BV/TV and Tb.n in the PTM of OVX rats. In addition, tanshinone increasedtrabecular thickness (***) whereas it did not alter MS/BS. Moreover, tanshinone had no effect on uterine weightand body weight of OVX rats. Estrogen treatment increased BV/TV and Tb.n and decreased OCS/BS, but, alsomarkedly decreased MS/BS and increased uterine weight in OVX rats. COnCLUSIOn: the current study demon-strated that the adequate supply of tanshinone prevented OVX-induced cancellous bone loss in rats through inhibi-tion of elevated bone resorption.

关键词： tanshinone cryptotanshinone 2-fluoro-17alpha-ethynylestradiol ovariectomy bone and bones osteoclasts osteoporosis histocytochemistry morphology

Dominant and recessive models reveal new candidate genes with bone geometry:meta-analysis of genome-wide association studies

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Dominant and recessive models reveal new candidate genes wit...

第十五次全国动物遗传育种学术讨论会

作者： Jiapeng Zhou~1,Lanjuan Zhao~2,Jian Li~3,Peng Xiao~2,Qin Zhang~1,Hongwen Deng~3 1.state Key Laboratory for Agrobiotechnology,Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology,China Agricultural university,Beijing,China 2.osteoporosis research center, creighton university medical center,omaha,ne,usa 3.departments of Orthopedic Surgery and Basic medical sciences, university of Missouri-Kansas City,Kansas City,MO,usa

Introduction Genome-wide association(GWA) studies have begun to apply to genetic researches and attempt to understand the undetermined and overwhelming majority of genetic variation accounting for human diseases,such ... 详细信息

关键词： human bone geometry genome-wide association meta-analysis

Association between eIF3α Polymorphism and Severe Toxicity Caused by Platinum-based Chemotherapy in non-Small Cell Lung Cancer Patients

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Association between eIF3α Polymorphism and Severe Toxicity ...

传承与发展，创湖南省生理科学事业的新高——湖南省生理科学会2011年度学术年会

作者： Xiaojing Xu1,Lifang Han1,Li Duan2,Yingchun Zhao3,Huaping Yang4,Boting Zhou5,Honghao Zhou1,Zhaoqian Liu1(1Institute of Clinical Pharmacology,Hunan Key Laboratory of Pharmacogenetics,Central South university,Changsha,Hunan 410078,China 2 department of Oncology,Zhongnan Hospital,Wuhan university,Wuhan,Hubei 430071,China 3 osteoporosis research center,creighton university medical center,omaha,ne 68124,usa 4 department of Respiratory Medicine,Xiangya Hospital,Central South university,Changsha,Hunan 410008,China 5 department of Pharmacy,Xiangya Hospital,Central South university,Hunan 410008,China)

Background Platinum-induced toxicity severely impedes successful chemotherapy in lung cancer *** excision repair(neR)pathway is considered as one of the major factors contributing to platinum side effects. Furthermore... 详细信息

关键词： eIF3α,non-small cell lung cancer(nSCLC),platinum toxicity,ototoxicity,nephrotoxicity,survival analysis

Effects of SCn1A Gene Polymorphisms on efficacy and safety of carbamazepine treatment on partial-onset seizures in Chinese Han Population

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Effects of SCN1A Gene Polymorphisms on efficacy and safety o...

传承与发展，创湖南省生理科学事业的新高——湖南省生理科学会2011年度学术年会

作者： Bo-Ting Zhou1,2,Qiu-Hong Zhou3,Guo-Liang Li4,Jian Qu1,Ding Liu5,Xiao-Jing Xu1,Lan-Juan Zhao6,Hong-Hao Zhou1,Zhao-Qian Liu1(1Institute of Clinical Pharmacology,Hunan Key Laboratory of Pharmacogenetics,Central South university Xiang-Ya School of Medicine 2department of Pharmacy,Xiang-Ya Hospital of Central South university,Changsha,Huan,China 3department of Endocrinology,Xiang-Ya Hospital of Central South university,Changsha,Hunan,China 4department of neurology,Xiang-Ya Hospital of Central South university,Changsha,Hunan,China 5department of neurology,third Xiang-Ya Hospital of Central South university,Changsha,Hunan,China 6osteoporosis research center,creighton university medical center,omaha,ne,usa)

Aims In this study,for rs3812718 G/A and rs2298771 A/G polymorphisms of sodium channel α subunit type 1(SCn1A)gene,we investigated whether SCn1A polymorphisms impacted the efficacy and safety of carbamazepine(CBZ)in ... 详细信息

关键词： SCn1A,genetic polymorphism,carbamazepine,epilepsy

Genome-Wide Association study Identified HMGn3 Locus for Spine Bone Size Variation in Chinese

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Genome-Wide Association Study Identified HMGN3 Locus for Spi...

中华医学会第六次全国骨质疏松和骨矿盐疾病学术会议暨中华医学会骨质疏松和骨矿盐疾病分会成立十周年

作者： Shu-Feng Lei~(1,2),Hui Shen~2,Tie-Lin Yang~3,Yan Guo~3,Shan-Shan Dong~3,Xiang-Hong Xu~3,Fei-Yan Deng~2,Qing Tia n~2,Yong-Jun Liu~2,Yao-Zhong Liu~2,Jian Li~2,Hong-Wen Deng~(1,2,4) 1 Laboratory of Molecular and statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education,College of Life sciences,Hunan normal university,Changsha,Hunan 410081,P.R. China 2 department of Biostatistics and Bioinformatics,School of Public Health and Tropical Medicine,Tulane university, new Orleans,Louisiana 70112,usa 3 School of Life Science and Technology,Xian Jiaotong university,Xian,Shanxi 710049,P.R.China 4 center of Systematic biomedical research,university of Shanghai for Science and Technology,Shanghai 200093, P.R.China

Bone size(BS)is one of major risk factors for osteoporotic *** variation is determined genetically to a substantial degree with heritability over 50%,but specific genes underlying variation of BS are still largely *** identify specific genes for BS in Chinese,initial genome-wide association scan(GWAS)study and follow-up replication study were ***

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Alcoholic hepatitis: the pivotal role of Kupffer cells

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World Journal of Gastrointestinal Pathophysiology 2015年第4期6卷 90-98页

作者： Duminda B Suraweera Ashley n Weeratunga Robert W Hu stephen J Pandol Richard Hu Suraweera Department of MedicineOlive View-UCLA Medical Center creighton university School of Medicine College of Arts and sciences the University of Pennsylvania department of Gastroen-terology and biomedical sciences Cedars-Sinai Medical Center department of Gastroenterology Olive View-UCLA Medical Center and David Geffen School of Medicine at UCLA

Kupffer cells play a central role in the pathogenesis of alcoholic hepatitis(AH). It is believed that alcohol increases the gut permeability that results in raised levels of serum endotoxins containing lipopolysaccharides(LPS). LPS binds to LPS-binding proteins and presents it to a membrane glycoprotein called CD14, which then activates Kupffer cells via a receptor called tolllike receptor 4. this endotoxin mediated activation of Kupffer cells plays an important role in the inflammatory process resulting in alcoholic hepatitis. there is no effective treatment for AH, although notable progress has been made over the last decade in understanding the underlying mechanism of alcoholic hepatitis. We specifically review the current research on the role of Kupffer cells in the pathogenesis of AH and the treatment strategies. We suggest that the imbalance between the pro-inflammatory and the anti-inflammatory process as well as the increased production of reactive oxygen species eventually lead to hepatocyte injury, the final event of alcoholic hepatitis.

关键词： Alcoholic liver disease Alcoholic hepatitis Macrop